Biotechnology Focus Podcast

Welcome back to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene. So, as many of you know, we are coming up to a very busy and exciting time of the year, as BIO is just around the corner! And this isn't just any regular BIO, this year marks the 25th anniversary in its inaugural location – Boston. It's four days chalked full of keynotes, receptions and networking opportunities that will leave you trying to catch your breath at the end of the week. But if that doesn't take your breath away, perhaps the performance by Diana Ross might at the largest BIO event of the year! 

But bringing the focus back to Canada, a lot has been going on in the last few weeks that is worth mentioning. Keep listening to find out! 

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In a world where artificial intelligence has begun to incorporate itself in everything from life sciences to cars, it should come as no surprise that South Korean tech giant, Samsung, is jumping in with both feet opening AI Centres around the globe, one of which just opened in Canada's most bustling city – Toronto. 

The opening of the Toronto AI Centre comes on the heels of the company's global announcement of two additional and newly established AI Centres in Cambridge, UK and Moscow, Russia as part of a new venture to tap into and contribute to the booming AI industry. The Toronto Centre will work in partnership with the company's Silicon Valley team to pioneer AI research and development for the region. 

Toronto has a rich history of innovation and discovery and is an ideal location for a vast amount of companies to call home. With access to key talent, Toronto is an idyllic place for research and development for speech recognition, where machine-learning technology was applied many years before it was widely applied to other fields. The vision is that the Samsung AI Centre will now serve a significant role in the advancement of AI with a focus on language understanding and computer vision technologies that will ultimately reduce the friction between the user and the device/service, whether it be mobile phones, TVs, appliances, or cars. 

Located in Toronto's downtown core at MaRS Discovery District, the new Samsung AI Centre is a part of a network of research Centres dedicated to research and development in the field of AI. The Centre is the second Samsung AI Centre to be established in North America, with the other in Mountain View, California. The North America AI Centres are led by senior vice president, Dr. Larry Heck, a renowned expert in machine learning for spoken and text language processing, who also co-leads the expansion of Samsung's AI Centres around the globe. 

The Toronto centre will be led by Dr. Sven Dickinson, newly appointed as the head of the Toronto lab, professor on leave and past chair of the Department of Computer Science at the University of Toronto. Dickinson is an expert in computer vision technologies, especially in the field of object recognition. He will play an integral part in Samsung's research of core AI technologies that entail language, vision and other multi-modal interactions. 

As one of the world's largest urban innovation hubs, MaRS Discovery district supports promising innovators and ventures tackling key challenges in the sectors of cleantech, finance & commerce, and work & learning. In addition, and importantly, the vast MaRS community fosters cross-disciplinary collaboration which drives breakthrough discoveries and new solution for global audiences. 

This announcement compliments earlier 2018 news of plans to launch additional AI centres in North America. Dr. Darin Graham will lead the opening of new labs in Canada as the head of Samsung's Canadian AI Operations. Graham also helped create the Vector Institute – the renowned Canadian AI research institute, as a member of the founding team. The opening of AI centres in Canada will allow Samsung to expand its outpost for industry collaboration and talent recruitment in the major AI hubs in North America. 

To date, Samsung has had remarkable success in leveraging Canada's unique R&D talents for global impact. The Company's Vancouver-based R&D centre has contributed to many in-market innovations and more than doubled its workforce, since opening with over 100 employees. With the addition of the AI centre in Toronto, the company plans to increase the R&D in Canada from current 100 to 200 in the near future. Additional developments and talent in Canada have been recognized through Samsung Electronics Canada subsidiaries, AdGear Technologies Inc. in Montreal and SigMast Communications Inc. in Halifax, Nova Scotia. 

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When it comes to what drugs get funded, how do provinces and the Canadian health care system decide which drugs to fund and which drugs not to? A team of University of Alberta researchers found that when a jury is made up of a cross-section of society and given proper information and context, people are willing to fund drugs and treatments for costly ultra-rare diseases, even at the expense of treatments for larger populations. 

An example would be a rare genetic disorder that robs men of sight by the age of 40. It affects one person in 50,000 and does not yet have a cure. But it does have a very expensive, unproven gene therapy that holds the promise of delaying the inevitable. 

Tania Stafinski, a researcher in the University of Alberta's School of Public Health and director of the Health Technology and Policy Unity says, "The fallacy is that these kinds of decisions are based on the greatest good for the greatest number. It's partly greatest need, partly what the gain looks like, partly the severity of the disease and partly the population affected. It is an interaction of all these things, but not whether it is utilitarian." 

To better understand the social values around spending on new technologies and commercially undeveloped "orphan drugs, Stafinski convened a pair of citizen juries that roughly matched the sociodemographic profile of people in and around Edmonton. 

Just like in a legal setting, Stafinski called witnesses that represented government, health-care providers and patients, and led the juries through different trade-off exercises and scenarios. For the most part, specific drugs and technologies were avoided to rid the study of any bias and allow jurors to focus more on the characteristics of the people and what could be achieved. 

The jury was put through seven trade-off exercises focusing on things that might matter to them, such as cost, the condition of the patient, what kind of technology is involved, how much improvement could be expected, and even caregiver burden. 

Despite the stakes, uncertainties around whether the technology would be able to fully deliver on its claims didn't play a significant role in decision-making. Even in cases, such as the gene therapy for vision disorder, where there was a risk the technology would fail, Stafinski found that jurors valued the information and innovation component of the research. 

Final decisions on what technologies and drugs to fund are currently made by a provincial review committee, guided by a pan-Canadian evidence review process that leaves it up to the provinces to take into account social and ethical implications. 

She says there are examples in the Canadian health-care system where a small gain for hundreds of thousands of people is implicitly sacrificed to give sufficient medical gains to a small group. One example is administering the flu vaccine—inhaled versus injected. 

Stafinski explains that although a large segment of society may prefer to have the inhaled version of the flu vaccine, with a few exceptions, policy-makers aren't spending the extra money for the inhaled vaccination, choosing instead to fund medications such as those that improve the quality of life for the 4,000 Canadians who suffer from cystic fibrosis. 

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A new study from The Ottawa Hospital is the first of its kind. The study suggests that treatment for erectile dysfunction coupled with a flu vaccine might be the solution to eradicating cancer cells after surgery. The study, published in OncoImmunology, shows that this unconventional strategy can reduce the spread of cancer by more than 90 percent in a mouse model. It is now being evaluated in a world-first clinical trial. 

Senior author Dr. Rebecca Auer, surgical oncologist and head of cancer research at The Ottawa Hospital and associate professor at the University of Ottawa says, "Surgery is very effective in removing solid tumours. However, we're now realizing that, tragically, surgery can also suppress the immune system in a way that makes it easier for any remaining cancer cells to persist and spread to other organs. Our research suggests that combining erectile dysfunction drugs with the flu vaccine may be able to block this phenomenon and help prevent cancer from coming back after surgery." 

The current study investigated sildenafil (Viagra), tadalafil (Cialis) and an inactivated influenza vaccine (Agriflu) in a mouse model that mimics the spread of cancer (metastasis) after surgery. The researchers evaluated these treatments by counting the number of metastases in mouse lungs. They found an average of: 

37 metastases with cancer cells alone 

129 metastases with cancer cells and surgery 

24 metastases with cancer cells, surgery and one of the erectile dysfunction drugs 

11 metastases with cancer cells, surgery, one of the erectile dysfunction drugs and the flu vaccine 

Dr. Auer is now leading the first clinical trial in the world of an erectile dysfunction drug (tadalafil) and the flu vaccine in people with cancer. It will involve 24 patients at The Ottawa Hospital undergoing abdominal cancer surgery. This trial is designed to evaluate safety and look for changes in the immune system. If successful, larger trials could look at possible benefits to patients. 

The researchers are excited about this research because it suggests that two safe and relatively inexpensive therapies may be able to solve a big problem in cancer. If confirmed in clinical trials, this could become the first therapy to address the immune problems caused by cancer surgery. 

Using a variety of mouse and human models, Dr. Auer's team has also made progress in understanding how erectile dysfunction drugs and the flu vaccine affect cancer after surgery. Normally, immune cells called natural killer (NK) cells play a significant role in killing metastatic cancer cells. But surgery causes another kind of immune cell, called a myeloid derived suppressor cell (MDSC), to block the NK cells. Dr. Auer's team has found that erectile dysfunction drugs block these MDSCs, which allows the NK cells to do their job fighting cancer. The flu vaccine further stimulates the NK cells. 

Dr. Auer stresses that although erectile dysfunction drugs and the flu vaccine are widely available, people with cancer should not self-medicate. Any changes in medication should be discussed with an oncologist. 

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Some of the hottest areas in biotech that are emerging and driving growth and investment are in the field of regenerative medicine and cell and gene therapy. There have been several acquisitions over the past year that really got the ball rolling with hopes to advance immunotherapies. Despite the curative potential, these therapies come with a hefty price tag and complex challenges. With the first immunotherapies to win regulatory approval in the United States, CCRM, a leader in developing and commercializing cell and gene therapies and regenerative medicine technologies, hosted a panel to discuss how we can bring these therapies to Canada. 

The panel represented a wealth of knowledge covering regulatory and hands on approaches to the subject. It was moderated by Michael May, president and CEO of CCRM, and consisted of Donna Wall, MD, section head, Blood and Marrow Transplant/Cell Therapy Program, The Hospital for Sick Children (SickKids); Justin Shakespeare, executive director, Oncology Business Unit, Amgen; Patrick Bedford, senior manager, Clinical Translation and Regulatory Affairs, CCRM; and Aaron Dulgar-Tulloch, PhD, director of Bridge, GE Healthcare Cell Therapy. 

There have been many decades of work in people trying variations of immunotherapy approaches and not getting a clinical signal. It was after researchers figured out T-cell biology and that they needed to bring not only the patients' T-cells right up against the tumour cell but also that they had to get the T-cell excited and activated to go into cell division. 

Donna Wall explains, "The first successful patient was only about six years ago. No question that the treatment can cure, as long as you take six years as to how long to treat a number of patients who otherwise have untreatable leukemia. That's the first type of patients that we have when we have a new treatment. We take the patients where we have nothing else to offer. A number of patients do not make it to the treatment because it takes a while to engineer the cells; a number of patients may not have a response to the treatment; and a number of them who go into remission may end up relapsing. But for the first time, there are many who are responding positively to treatment and are not showing signs of leukemia." 

This is still in a very early-stage as of yet. It is not a one-and-done type of treatment. In order for this to work, the most common CAR-T product removes the cancer cells as well as the patient's B-cells lifelong – giving them an immune deficiency. It is complex and comes with its own set of issues that may put up to 40 per cent of patients into intensive care for side effects of the CAR-T treatment. The treatment should not be taken lightly and will not be handed out over the counter. 

The cost of the treatment is another factor entirely. Like anything new, cost is initially high but is expected to come down over time. It is a huge cost for a company to invest in and build the infrastructure that needs to be actualised as well as looking at regulatory costs. If the treatment becomes more mainstream, its costs pose another issue, as the health care system has not been designed to handle a large influx of big-ticket cases. 

Patrick Bedford, CCRM, states, "There's value in when you want to pay for something, but can you actually pay for it today is the real question. The number of drugs over $50,000 since a decade ago has gone from two to 20, and the drugs targeting orphan or rare diseases has all skyrocketed. There might not be a lot of people in each of these disease populations, but there are a lot of disease populations. So, the idea of affordability is really important. There are some new discussions right now about how to pay for these, like money back, or paying for performance type things, or rather than paying it all at once, pay three, four years later. There are a lot of ideas right now about how to afford the population if we choose they are worth the value to pay for." 

These are living drugs and therapeutics that have a very complex process on the manufacturing side as well as the rest of the supply chain. Each treatment batch is tailored to the patient. Many treatments start as autologous, but there are groups that are currently working on making this into more of an allogeneic process. 

Aaron Dulgar-Tulloch explains, "Everyone wants to go from autologous to an allogeneic model. Every commercial entity would prefer to be in that allogeneic scenario because it is much better realised, there's simplification in the supply chain, logistics, and the scale of benefits. We're already starting to see groups trying to turn autologous into an allogeneic process. I think we will see more groups coming in with successful approaches to a more allogeneic or classical model." 

However, the playing field is changing as more treatments are reaching approval on a shorter timeline and with less clinical data. Even though much of that data presented to the regulators have been enormously successful, it is not typically a fast-moving field. This leaves the regulators to navigate through the treatments and do so in a receptive and responsible manner. 

Since these therapies are still so new right now, it has put a particular strain, even on a global scale, to find individuals with expertise in scale up and industrial manufacturing coupled with biological cellular experience. 

Dulgar-Tulloch explains that Canada in particular is feeling the pain from that, in that they don't have a lot of the manufacturing infrastructure in Canada to pull from, and what Canada has is still heavily engaged in the bioprocess space.  

CCRM has a centre devoted to improving the cell manufacturing process and is attracting international attention from companies who are looking for CCRM and GE's expertise in process development. This work also feeds into the Good Manufacturing Process (GMP) facility that CCRM is building that provides space for therapeutics companies to run phase I and II clinical trials. 

What it all boils down to when it comes to markets like Canada, is that timing is often regulatory-driven and balancing considerations as to where manufacturing is and how to support the local market, with timing as an implication on the pricing perspective. Canada needs to leverage its strengths on the clinical side so that we extract value from manufacturing and ultimately deliver these products to patients for commercialization. 

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Well that wraps up another episode of Biotechnology Focus radio! As always, we have all the stories online and in full to fish through at your leisure at biotechnologyfocus.ca. If you have a story idea or wish to make a comment, please email me at [email protected]. But until the next time, enjoy the spring weather and for those attending the BIO International Convention this year, good luck and enjoy! From my desk to yours – this is Michelle Currie. 

087 | Shifting thoughts and actions  

Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene. This week sheds light on antibacterial resistance and how that will change the course of the world on a widespread scale if our patterns do not change, how pharmacogenomics has become a new era in precision health, and how there may be a link between poor muscle health and type 1 diabetes.  

Listen on to find out more! 

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Ever consider a world where surgery was no longer an option? It is the unfortunate truth that if society does not slow the progression rate of antimicrobial resistance, life as we have come to know it will no longer be our future. 

Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses, and fungi. Without such means of effective treatment, it will compromise therapies that have been used for decades in healthcare and puts society in a very precarious position. Treatments such as major surgery or chemotherapy may fade into the background. 

As we stand on the precipice of a post-antibiotic apocalypse, this global concern has researchers all over the world clamouring to find a solution before this issue gets out of hand. Kevin Schwartz, an infection prevention and control and antimicrobial stewardship physician from Public Health Ontario is one of those researchers seeking a strategy. 

Dr. Kevin Schwartz says, "Antimicrobial resistance is going to be one of the biggest future challenges and it really threatens the way that we practice medicine. We take for granted some of the modern advances of technology that we will really jeopardize if the trend of antimicrobial resistance continues." 

Antimicrobial resistance happens when microorganisms change from exposure to antimicrobial drugs. It is a natural process that happens over time, but, unfortunately, that timeline has been accelerated due to the misuse and overuse of antibiotics in people and animals. Whether it stems from prescribing patients' antibiotics for things such as a cold or flu, or when they are given as growth promoters in animals or used to prevent disease in healthy animals, the truth is that we need to find a solution to contend with these "superbugs" – and fast. 

Antimicrobial resistant-microbes are found in people, animals, food, and the environment (water, soil, and air.) They can transfer from person to person, from person to animal and animal to person – that includes food of an animal origin – and is present in every country worldwide. 

It's such a huge global overwhelming problem. From hospital settings to non-hospital settings, using more antibiotics than we probably need to. There are a variety of reasons for that. Antibiotics are effective and life-saving, and often patients present with unclear diagnoses so antibiotics are often used to be on the safe side and so we are not missing a potentially treatable illness. 

Schwartz adds that the fields of antimicrobial stewardship are trying to develop ways to help physicians and prescribers use the antibiotics more appropriately. There's probably depending on the study and the area being treated, inappropriately prescribed 30-50 per cent of the time. So, there is lots of room to improve our antibiotic use.  

However, there isn't one strategy that is applicable across all patient settings and types of conditions and there is a lot of variability as to how antimicrobial stewardship can be implemented. For instance, the approach to improving antibiotics is going to be quite different depending on the setting. Some examples would be the difference in the intensive care unit compared to hospitalized patients, compared to patients treated in the emergency room, compared to patients treated in family doctor offices. 

Schwartz focus is mainly on the out-patient setting. So, how can we approach family physicians and community prescribers to use antibiotics more appropriately? Some of the strategies to do this would be to provide feedback to family physicians. Some of the stuff that they are scaling up to do is to be able to give doctors some comparisons and feedback. For example, how much antibiotics are they prescribing compared to their peers? Then by identifying those doctors that are high prescribers we can have a significant impact to decrease overall prescribing. 

He goes on to suggest that there are other simple measures that can be implemented, such as a study done in the US that monitored how a poster mailed to family doctor clinics and signed by the corresponding physician with the intent to use antibiotics appropriately displayed in the waiting room affected overall usage. The study showed that even this simple measure decreased over-prescribing by 20 per cent. 

Public Health Ontario have done something similar in Ontario over the last year, partnering with Choosing Wisely Canada, an organization aimed to decrease waste and improve healthcare efficiency. So, they sent the poster to about 13,000 doctors in Ontario to hang in their offices for a similar purpose. 

There are discrepancies in the system across the country, however, about the amount of antibiotics being prescribed by population and contrasting health regions. This could be due to the variance of the practice of physicians in different geographical locations. Some prescribe more, while others tend to prescribe less – allocating education and feedback as one of the best means to observe overprescribing. 

There are notable differences between urban and rural environments prescription and usage, but through multi-variable modelling incorporating these variables as predictors, it is still undetermined why some prescribe more over others. 

Schwartz says, "We want to make sure people are using the appropriate medicine for the appropriate condition. So, we're not using overly broad, overly toxic medication when we do not need to." 

A study that was done in the UK highlighted what would happen if the course of action did not change over time. They estimated that there are roughly 700,000 deaths a year from antibiotic-resistant infections and that if we do not do anything by the year 2050, that number could reach a high of 10,000,000. To put that number in another light, the death toll will surpass cancer and motor accidents combined. 

By weight, most antibiotics are used in animals, not in humans, and there's lots of antibiotics in the environment and in other parts of the population. So, there's all these different approaches where we need to combine – animal veterinary health with human health with environment – and all these different things need to come together so that we can mitigate antibiotic exposure and an element of resistance. 

The importance of this issue can not be understated. All the advances that have been accomplished in health care will be for naught if antimicrobial resistance continues down this path. Successfully taking care of premature babies, organ transplant, bone marrow transplant, and complex cancer therapies are all prime examples of procedures that will become incredibly difficult or impossible to achieve. They all rely on the fact that we can treat the complications that go hand in hand with the procedure – namely infections. These patients are more susceptible to bacterial infection, and without effective antibiotics the procedure may be too risky. 

If you think back to the way things were during WWI when there was no antibiotics when even a small wound in battle could be life-threatening or limb-threatening. We really take for granted what we now consider a simple condition, where in the past was life-threatening. Schwartz says they will become life-threatening again in the absence of effective antibiotics for these problems. 

Physicians and dentists are examples of prescribers that need to prescribe antibiotics appropriately, and for the public to have an awareness of the risks of taking antibiotics unnecessarily over time. This awareness needs to be spread before the world turns into a post-antibiotic era. Antimicrobial resistance is an inevitable process. The bacteria are alive, and they will evolve to survive. 

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Genomics is driving a paradigm shift from a disease-oriented health-care system to one that is more precise, personalized, predictive, preventative and cost effective. 

Advancements in technology are helping make genomics more affordable and accessible than ever before. Likewise, societal attitudes toward genomics in clinical care are shifting. We are no longer asking 'if' genomics should be integrated with clinical care. Instead we are asking 'when' and 'how' we can use genomics to benefit as many people as possible. 

With a vision to advance the use and application of genomics in clinical practice, Genome BC has invested almost $370 million in over 160 research projects. Genomics research is already saving lives and improving health outcomes and disease management for patients touched by cancer, heart disease, autism, epilepsy, rare diseases and other debilitating diseases. As genomics research moves from the bench to the bedside, clinical applications of genomics will affect many areas of medicine over the next 10-20 years, improving disease prevention, diagnosis, and treatment, as well as informing our approaches to wellness, nutrition, and public health. 

Genome BC has had a long-standing interest in, and support for, a particular aspect of precision health called pharmacogenomics. Since 2004 we have invested in a number of projects analyzing the unintended side effects of medication, known as adverse drug reactions (ADRs). The discipline of pharmacogenomics, identifying gene variants that predispose people to serious side effects of medications or that alter the way your body will respond to, or metabolize, certain drugs, is being applied to improve the safety and efficacy of many therapeutics and treatments. We are funding teams across different levels of research in this critical field: in the hospital alongside clinicians, in the pharmacy and with primary care physicians. 

At the hospital level Dr. Bruce Carleton and his team are working to prevent ADRs by developing laboratory tests to predict the likelihood of a childhood cancer patient developing an ADR and tools to incorporate these tests into clinical practice. At the pharmacy level another group, led by Dr. Corey Nislow and the BC Pharmacy Association, has developed a community pharmacist-based approach to pharmacogenomic testing wherein a patient's saliva is tested for genes that will predict adverse reactions to commonly prescribed drugs. Finally, at the family physician level Dr. Martin Dawes and his multi-disciplinary team of doctors, pharmacists, and epidemiologists have developed TreatGx, a unique medication decision support system. Using the highest levels of evidence, TreatGX identifies personalized medication options for multiple common conditions. The options are presented to the doctor in an easy-to-read format with helpful information such as dosing instructions, potential adverse reactions, and medication cost comparisons. 

Each of these research teams are bringing new understanding to the table, as well as integrating their work for maximum benefit to patients. 

The goal of pharmacogenomics is to improve patient outcomes. In order to implement this tool effectively we must: 

Validate the efficacy of genomics applications in day-to-day patient care 

Ensure we are increasing value to patients and lowering costs 

Identify and provide information related to diagnostic criteria and provide the relevant pharmacogenomics test(s) 

Develop guidelines to help clinicians use these tests 

Change perceptions for healthcare professionals and patients 

Genome BC is working closely with the provincial government, universities, clinicians and other stakeholders to advance the clinical use of pharmacogenomics. 

Canada is not the only country working to implement precision health- there is a global effort working towards a common goal. Momentum is building and there are success stories of clinical implementation of genomics happening in real time around the world. In BC there has been a critical change in the Hereditary Cancer Screening Program at the BC Cancer Agency because of a gene panel test that enables clinicians to test for more than a dozen of the most common mutations all at once, rather than one-by-one. This test enables people to learn what cancers they may develop, how often to have medical follow-ups, what cancer screening to get and whether there are preventive lifestyle factors that might mitigate the risks. Wait times for this test have gone from several months to a few weeks and BC Cancer is even helping other provinces clear their backlog. The hereditary cancer panel is now being reimbursed by the BC provincial government and has been fully integrated in clinical practice. 

Clinical practice has begun to incorporate genomics technology and applications. Ultimately physicians will have practice guidelines to best move patients along a treatment pathway that is best suited to their own genetic makeup. 

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A recent study coming out of the labs of McMaster and York Universities have found that there may be a link between poor muscle health and type 1 diabetes – even among the youth. 

The research team analyzed muscle biopsies of young adults with and without Type 1 diabetes who exceed Diabetes Canada's recommended weekly levels for physical activity. 

The researchers found structural and functional changes in the power generation parts of the cell, or mitochondria, of those with diabetes. Not only were the mitochondria less capable of producing energy for the muscle, they were also releasing excessive amounts of toxic reactive oxygen species, related to cell damage. 

These changes have the ability to affect metabolism – the chemical processes that occur within a living organism in order to maintain life – resulting in a greater difficulty controlling blood glucose, and if unmanaged, could accelerate to a disability. The study findings add poor muscle health to the list of better-known complications of Type 1 diabetes, including nerve damage, heart disease and kidney disorders. 

Thomas Hawke, corresponding author of the study and a professor of pathology and molecular medicine at McMaster says, "Now we know that even active people with diabetes have changes in their muscles that could impair their ability to manage blood sugar. Knowing in the long term that this could contribute to faster development of disability, we can start to address it early on." 

 Skeletal muscle is the largest metabolic organ and is the primary tissue for clearing blood sugar after eating a meal, so it is necessary to keep muscle as healthy as possible. 

With regular aerobic exercise, mitochondria in muscle increase to therefore help muscle cells use more glucose and become more efficient. 

The researchers believe these dysfunctional mitochondria are what's causing the muscle to not use glucose properly and to also damage muscle cells in the process and were surprised to see the muscles were this unhealthy in young adults with Type 1 diabetes who were regularly active. 

Researchers say while further study is needed, revising evidence-based exercise guidelines, specific for those with Type 1 diabetes, may be required to keep them in the best health. 

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Well that wraps up another episode of Biotechnology Focus radio. Thanks for checking in! If you would like to read the stories in full, please visit our website at biotechnologyfocus.ca. From my desk to yours – this is Michelle Currie.  

086 | Paving the way of the future   

Welcome to another episode of Biotechnology Focus radio! This week Toronto got their socks knocked off by an announcement from Sanofi; a Chinese company expresses interest in some of Canada's regenerative medicine technologies; the scope of clinical trials in Canada is divulged at the recent Clinical Trials Ontario conference; and Shana Kelley and her team from the University of Toronto use new technology to essentially 'find a needle in a haystack' when it comes to prostate cancer. Keep listening to hear the latest news of Canada's biotech scene! 

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French company Sanofi announces one of their largest investments ever in a single building and knocks the socks off the Toronto life sciences community. Sanofi announces that they are investing €350 million (C$500 million) into their Toronto facility to significantly increase capacity to meet the growing demand for pediatric and booster vaccines and demonstrate their commitment to innovation and leadership in global health. 

The announcement was held at Sanofi Pasteur's Canadian headquarters in Toronto and was joined by the Honourable Navdeep Bains, Minister of Innovation, Science and Economic Development, and the Honourable Steven Del Duca, Minister of Economic Development and Growth. 

Canada has a strong legacy in the research and development of vaccines. With this investment, Sanofi is renewing their longstanding commitment to making Canada central in the effort to protect and improve human health across the globe. Vaccines save three million lives every year and this new facility will be one step closer to a world where no one suffers or dies from a vaccine-preventable disease. 

The new facility will allow Sanofi Pasteur, the vaccines global business unit of Sanofi, to meet the growing demand of five-component acellular pertussis (5-acP) antigen. The building itself is expected to be completed within three to four years, a year or two to get the quality management system up and running, and a year or two to do product development and testing. The site will be equipped to produce the antigens used in the diphtheria and tetanus vaccines. 

Philippe Luscan, the executive vice president of Global Industrial Affairs, Sanofi says that this project is one of the most important investments for the Sanofi global industrial network. It demonstrates the continued commitment to manufacturing excellence and to better serving their vaccines portfolio to people all over the world. 

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New opportunities are arising at every turn for the regenerative medicine community. Research is at the tip of the iceberg, but a company in British Columbia isn't waiting for the ice to melt. RepliCel, a regenerative medicine company, has been developing autologous cell therapies to treat conditions linked to the deficit of healthy cells required for normal function and healing. Their cell therapies are designed to treat chronic tendinosis, UV-damaged or aged skin, and pattern baldness as an alternative method to surgery, pills, and chemicals. 

Recently, YOFOTO, one of China's largest health and wellness companies announced its intention to invest significant financial backing into the company to market RepliCel's tendon repair and skin rejuvenation products – and they are not the only one – Shiseido, another giant, has been developing RepliCel's hair regeneration technology for the Asian market. 

Last year hit significant milestones for the company with production of the first fully functioning prototypes of their next generation dermal injector that is optimal for the delivery of injectables into the skin. With patents already issued in the United States and in Europe, the functioning prototypes allow RepliCel to display the applications of the device with other potential partners as they move forward at finalising the mold for the commercial-ready devices. 

Last year also saw new clinical data produced on all three biologics programs – thinning hair (androgenic alopecia), aging/sun-damaged skin, and chronic tendinopathy (Achilles Tendinosis). The phase 1 clinical data demonstrated overwhelming product safety and highly encouraging signals of product efficacy to regrow hair, rejuvenate skin, and regenerate tendon tissue. 

In 2013, RepliCel executed a co-development and licensing agreement with Shiseido that covered all of Asia for their hair regeneration program. Now, with the potential for another deal emerging in Greater China, we have real opportunity to leverage these partnerships to be a leader in regenerative medicine platform across Asia. 

According to Brad Loncar, who recently launched a China BioPharm Index Fund, following the success of his Cancer Immunotherapy Fund, the biotechnology and pharmaceutical sectors are headed for exponential growth in the next few years and cell therapies are a significant focus in Greater China where he believes they are "ahead of the curve". 

Indeed, last month, the Chinese government unveiled its Made In China 2025 industrial plan in which it laid out a strategy for revolutionizing the Chinese biopharmaceutical industry through major investments in the sector and its supporting infrastructure. 

It is a very exciting time for RepliCel as they move forward with a CE mark for their device in Europe and their potential expansion in Asia, as well as refining their US strategy for the launch of their dermal injector. With fascinating development projects in queue and continuing to look for the right opportunities, there will be substantial progress that will come from this innovative regenerative medicine company in the near future. 

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It would be too easy to say that the recent CTO 2018 Clinical Trials Conference was an immense success – but it was. A sold-out event with 400 people speaks for itself. It was held in Toronto at the Sheraton Centre Hotel over two days chalked full of intrinsic speakers and panels discussing clinical research, clinical trials, and patient engagement. 

The first day brought wonderful opening remarks from the Honourable Reza Moridi, Minister of Research, Innovation and Science, and was followed by Brian Goldman as the morning's keynote speaker. 

Brian Goldman is an ER physician, author and radio broadcaster of CBC's White Coat, Black Art but chose to direct his keynote towards clinical trials in the age of disruption. Disruptive innovation has become a powerful change in health care, amongst many other industries. He defined exactly what disruptive innovation was with recent examples and its potential implications in health care – clinical trials, big data, clinical research. 

To kick off the first panel was Jason Field, president and CEO of Life Sciences Ontario as a moderator of the evolving clinical research environment. The panel facilitated discussion on how to adapt to changes and how patients, health care and the economy will be impacted now and in the future. 

As the day progressed there were speakers touching on future strategies, why Canada has a health care system, the misalignment of evidentiary interests and clearing the path ahead. An engrossing one-on-one interview after lunch with Francis Plummer, professor of medicine and medical microbiology from the University of Manitoba about a lesson in preparedness and how his work with the Ebola vaccine was a prime example of pre-empting what may happen, so that when and if it does, society will have a cure or at least a way to face it. 

Clinical trials simply do not happen without participants, so the second panel brought patients and caregivers of patients to the stage to share their stories and experiences. They brought to life what the health care community works for and to and their advice on helping others find and join a clinical trial was instrumental. 

The second day did not disappoint. Robert Bell, Minister of Health and Long-Term Care gave the opening remarks and welcomed the keynote speaker Ken Getz, director of sponsored research programs and research associate professor from the Tufts Center for the Study of Drug Development. Coincidently, he was also the keynote speaker at the very first Clinical Trials Conference that CTO put on a few years back; allowing him to describe first-hand how much it had grown and the benefits and impact this conference has on the clinical trials environment. He examined the current global operating environment for clinical research and specific areas where patient engagement practices and initiatives are being implemented. 

Patient engagement with clinical trials remains a hot topic and largely uncharted territory. The first panel explored these models of patient engagement to give a voice to patient perspectives, quality of life values, and treatment experiences so that the health care system can get access to the drugs patients need sooner and create more robust trials and outcomes. 

Following that, Molly Shoichet, Ontario's first Chief Scientist was the interviewee of the day and went into detail about Canada's research strengths, her aspirations for Ontario and Canada, and the innovation economy. 

The remaining panels covered current interests such as big data in healthcare to advance opportunity and mitigate privacy risks, and how to advance ways to streamline the conduct of clinical trials and make Ontario and Canada a better place to have them executed. They engaged the audience in fruitful discussions and answered many burning questions from the listeners. 

The two days compressed a wealth of knowledge, aspirations, and innovative ideas for the future of clinical trials in Ontario and Canada and left guests with an eagerness to start down that road. 

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Researchers at the University of Toronto have developed an innovative technology to identify which patients might not respond to standard therapy for prostate cancer before it is delivered from a "liquid biopsy". 

Prostate cancer is the most common cancer in men (excluding non-melanoma skin cancers) and third leading cause of death in Canada, according to the Canadian Cancer Society 2017 statistics. While several viable treatment options for prostate cancer exist, many men affected with prostate cancer will not respond to first-line treatments. 

Shana Kelley, a professor at the University of Toronto divulges that screening for drug resistance is key to improving treatment approaches for many cancers. It is important for patients not to be on a therapy that won't help them and it's also important for health-care systems to avoid, whenever possible, delivering ineffective treatments. 

Creating an option for a "liquid biopsy" via a blood test instead of more invasive alternatives is a step in the right direction and will save time, money, and recuperation time. 

Kelley, lead investigator on the study published in Nature Chemistry, explains how her team has advanced a completely new approach using magnetic nanoparticles with DNA capture probes on their surface that can target circulating tumour cells (CTCs) in blood samples to see if the cells contain biomarkers associated with drug resistance. 

The team traps the individual magnetized cells in a microfluidic device built in the lab, isolating them from all the other cells in the sample and allowing them to perform highly sensitive analysis. The cells with the highest magnetic content will also have a high messenger RNA expression for the biomarker associated with drug resistance. This means that patients with high messenger RNA expression should be considered for other therapies because they won't respond to the first-line treatment. 

Being able to access the circulating tumour cells  CTC cells is critical in the fight against cancer, as they carry information from the primary tumour that will divulge the best form of treatment for the patient. They are, however, outnumbered by a billion-to-one by normal cells in a patient's blood making catching them a very daunting task. 

In 2016, Kelley and her team published a study in Nature Nanotechnology that first introduced the microfluidic device and how it could be used to trap and analyze circulating tumour cells CTCs. The current study builds on this work by further targeting a specific biomarker within the circulating tumour cells CTCs. 

The blood samples analyzed were collected from a small cohort of patients undergoing treatment for metastatic prostate cancer. In 10 of the patients tested, circulating tumour cells CTCs were visualized but only four of the patients exhibited the biomarker associated with drug resistance. This finding demonstrates that the new method can provide both a circulating tumour cells  CTC count and an analysis of the clinically relevant biomarker. 

"We are very excited because this is like finding a needle in a haystack," says Kelley. "It paves the way for a straightforward and personalized screening tool that allows clinicians to see if a patient will respond to therapy or not. Our method is also rapid, accurate and inexpensive, which gives it real potential for clinical uptake." 

Further studies need to be conducted to ensure consistent findings. Kelley and her team would also like to take this technology and expand it to other forms of cancer and disease. 

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Well that's it for another episode of Biotechnology Focus radio! To read the stories in full check out our website at biotechnologyfocus.ca. Thank you for listening and have a great week ahead! From my desk to yours – this is Michelle Currie.  

085 | When it sounds more sci-fi than fact 

Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on what's happening on the Canadian biotech scene! This week we have some revolutionary research happening at the Centre for Drug Research and Development that sounds more sci-fi than fact, a treatment that allows the patient to breathe life back in, therapy that fits like a glove, and an over-the-counter drug that may be able to ward off Alzheimer's disease. Listen in to find out more! 

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Empirical observations over the past many decades have suggested that certain types of virus infections could lead to cancer regression. 

However, the use of so-called oncolytic viruses (OV) with the intent to treat cancer had been met with skepticism. Now, thanks to technological advancements in genetic engineering and virus manufacturing, oncolytic virotherapy has gained considerable attention and demonstrated significant, though perhaps limited, clinical successes.  

The Centre for Drug Research and Development (CDRD) have been working on ways to potentiate the utility of oncolytic viruses for cancer therapy in the hope that one day these strategies may be able to eliminate, or at the very least significantly reduce the need for traditional cytotoxic chemotherapy. Reducing the use of toxic treatments that impair the patient's immune system is expected to lead to better overall survival and quality of life for countless cancer patients. 

Dr. Ismael Samudio, Head of Biologics at the Centre for Drug Research and Development, has been preoccupied on how best to translate oncolytic virus strategies to the clinic, and in particular how to make these viruses work better in combination with targeted agents regardless of whether they are small molecules or antibodies. As Samudio explains, "We are cognizant that such a thing as a magic bullet for cancer is unlikely to exist. Pre-empting that, our work on oncolytic viruses is really trying to find the tools that we could take to the clinic (small molecules, antibodies) to make these agents successful in more cancer patients." 

Oncolytic viruses are a very powerful way to combat cancer. They are mostly genetically engineered to specifically target and kill cancer cells, without having an adverse reaction to the patient. They are also known for inducing an immune response against the cells they infiltrate. 

Currently, the Centre for Drug Research and Development is working with two distinct types of oncolytic viruses. One of them is the precursor of Maraba – a potent engineered virus currently in clinical trials. The Centre is not aiming to treat one particular type of cancer and hopes that their research will effectively work in multiple tumour types. 

Tumour cells, in general, have defective antiviral responses, and that's why oncolytic viruses preferentially infect them. Cancer cells do not like to stop making proteins. They're constantly growing and constantly making proteins. Normal cells have mechanisms that stop uncontrolled growth and protein synthesis. Because those mechanisms are defective in cancer cells, viruses infect them and they don't have a way to shut down the production of the virus, resulting in massive viral expression and death of the infected tumour cells. Some cancer cells are more sensitive than others to oncolytic viruses, and understanding how to improve the efficacy or these biological agents is paramount to their success in the clinic. 

The Centre so far has seen successful infection in every single cancer line that they have tested. Some cancer cells, however, tend to be able to escape death induced by the oncolytic virus, and thus in collaboration with several researchers, the centre for drug research and development is developing strategies to increase infectivity and engagement of the immune system. 

The Centre doesn't expect that there's going to be infection of normal tissue. Nonetheless, they remain focused on delivering the treatment to where it needs to go – the tumour. There is no reason if your heart is healthy, or your kidney or liver, to expose those organs to our chemo-biological interventions – whether small molecules or antibodies – and reduce the safety of the approach. They want to make sure that those interventions go to the tumour tissue. 

The centre expects for some of these efforts to take at least ten years to reach the clinic. Drug development can be a very daunting process, and of course, scientists and clinicians want to make sure it passes all safety and efficacy standards. The centre for drug research and development is a unique organization that focuses on a number of therapeutic areas, including cancer, auto-immune diseases, infectious diseases, neurodegenerative diseases and neurobiology in general. The knowledge gained at the Centre through innovative approaches, outside-the-box thinking, and cross-pollination of disciplines will ultimately lead to life-saving therapies. 

Oncolytic viruses are such an amazing tool. They can, directly and indirectly, inhibit cancer progression, and I expect them to eventually become a mainstay in cancer therapy. 

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There has been substantial research coming out of the woodworks from across the country in so many areas of health. But, when you are living with a disease and finally find that medication which makes you feel like yourself again, there is truly nothing like it. 

This was the case for Jennifer Falkiner. She had been diagnosed with asthma in her thirties and that progressed over time to severe asthma. Even the simple things we all take for granted became difficult, and little joys such as going to the movies, or having a solid nights sleep were taken away from her. 

It is only now participating in an innovative clinical trial for severe uncontrolled asthma with the use of Fasenra – a respiratory biologic – and the research of Dr. Mark Fitzgerald, primary researcher of the study, that her quality of life and her motivation has returned. "It has been a transformation," Jennifer says. 

In the beginning, she wasn't aware that she even had asthma. Starting as just a respiratory infection, her doctor gave her antibiotics and a puffer, but the infection was persistent and happened again and again. It was only upon going to another doctor that she was informed that she had asthma. 

Over the years, Jennifer was put on a slew of puffers and medications and yet she still could not stop coughing – making social life, family, and work scenarios trying, and arduous at times. 

Jennifer told me, "When I was much younger, before the asthma hit, I used to go tobogganing with my children. Then, I had grandkids come along and I couldn't do that – but now I can. I got on this drug trial and now nothing stops me." 

The CALIMA trial was one of three pivotal trials to reduce severe exacerbation requiring prednisone and has shown a 50 per cent reduction in patients who had the active treatment in lieu of the placebo. Fasenra is the only respiratory biologic that provides direct, rapid and near-complete depletion of blood eosinophils from the first dose. 

Around the world, asthma affects 315 million people, including an estimated 3 million Canadians. Roughly 250,000 Canadians live with severe, uncontrolled asthma, which can have a debilitating impact on lung function and quality of life. 

Many of the current medications also come with countless side effects, that may deter the people who need the medication from taking it at all. Prednisone, for example, has been known to affect sleeping patterns, weight gain, severe depression, bloody or tarry stools, slow wound healing, dizziness – just to name a few. Fasenra, on the other hand, has had minute reported adverse reactions and is taken every eight weeks after the initial three doses. 

Dr. Mark Fitzgerald hopes that in the future there will be blood or sputum tests to better identify the treatment that will work for each individual. We're at a very exciting stage because, hopefully, these drugs will not only be used in patients with severe disease but also can be used earlier in the patient's history of asthma to maybe modify the trajectory and prevent the progression to more severe disease. 

Fasenra has been approved by Health Canada and represents a significant milestone for severe eosinophilic asthma patients, finally offering a new treatment option to help manage their condition. 

The change for Jennifer has been dramatic. Going from a place where walking in the heat, scents, and the constant fear of the inability to breathe depicted what she could and could not do with her life, to now swim, skate, kayak, and play with her grandkids – she has never looked back. 

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Researchers at Western University have developed custom-fit gloves to help control tremors in patients with Parkinson's disease. Not only does this glove help give them some sense of normality again, but it gives them their independence back as well. 

Parkinson's disease is a long-term degenerative disorder of the central nervous system that tends to affect the motor system the most. The disease progresses slowly over time, and is best exemplified through constant shaking and rigidity. Eventually leading to difficulty walking, swallowing problems and other health conditions. Symptoms may vary from patient to patient. 

Anybody with Parkinson's that has tremors have them in their entire body, but it's the ones in their fingers that really prevent them from performing the activities of daily living. 

The problem with a lot of the devices that are currently on the market is that they restrict movement in general, which still makes the tasks at hand hard to do. In the worst-case scenario, it can even suppress movement at the level of the elbows or wrists that exacerbates the tremors in the fingers. 

The design model of the glove uses a system of sensors that track voluntary movements and separates them from involuntary tremors. The gloves will then suppress the tremor to allow fluid motion of movement. The current prototype glove was created for the left hand of student Yue Zhou, who used 3D printing to design a custom fit. 

The team is also working on improving the glove's hardware to make it more practical to wear, including reducing the size of the glove's controller and improving its battery system. Once these pieces are all in place, they hope to find commercial partners to bring the gloves to the market. 

If effective, this could dramatically change the lives of people living with Parkinson's disease, allowing them to do daily tasks many people take for granted. 

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As the general population of the world ages and as diseases like dementia and Alzheimer's become ever more prevalent, the hunt is on to discover a way to slow their progression or stop it entirely. 

A Vancouver-based research team led by Canada's most cited neuroscientist, Dr. Patrick McGeer, is now suggesting based upon his empirical research, that if a daily regimen of non-prescription NSAID (nonsteroidal anti-inflammatory drug) ibuprofen was started early enough it can prevent the onset of Alzheimer's disease. 

This study spells out a simple solution to a vastly complicated neurocognitive impediment. According to the Alzheimer's Disease International's World Alzheimer Report 2016, the disease affects 47 million people worldwide, costs the healthcare system more than US$818 billion per year and is the fifth leading cause of death in people over the age of 65. With Canada currently sitting around 560,000 people – a figure expected to rise to 937,000 by 2031 – there is no time to waste. 

Dr. McGeer, who is president and CEO of Vancouver-based Aurin Biotech, and his wife, Dr. Edith McGeer, are among the most cited neuroscientists in the world. Their laboratory is world-renowned for their 30 years of work in neuroinflammation and neurodegenerative diseases, particularly Alzheimer's disease. 

In 2016, McGeer and his team announced that they had created a simple saliva test that can diagnose Alzheimer's disease as well as predict future onset. The test is based on measuring the concentration of the peptide amyloid beta protein 42 (Abeta42) secreted in saliva. In most individuals, the rate of Abeta42 production is almost very similar regardless of sex or age. However, if that rate of production is two to three times higher, those individuals are inclined to develop Alzheimer's disease. That is because Abeta42 is a relatively insoluble material, and although it is made everywhere in the body, deposits of it occur only in the brain, causing neuroinflammation, which destroys neurons in the brains of people with Alzheimer's disease. 

Contrary to the belief that Abeta 42 is only produced in the brain, Dr. McGeer's team demonstrated that the peptide is made in all organs of the body and is secreted in saliva from the submandibular gland. As a result, with as little as one teaspoon of saliva, it is possible to predict whether an individual is fated to develop Alzheimer's disease. This provides the patient with the opportunity to begin taking early preventive measures, such as consuming over the counters like ibuprofen. 

Dr. McGeer explains that what they've learned through their research is that people who are at risk of developing Alzheimer's exhibit the same elevated Abeta 42 levels as people who already have it; moreover, they exhibit those elevated levels throughout their lifetime so, theoretically, they could get tested anytime. Knowing that the prevalence of clinical Alzheimer's Disease commences at age 65, they recommend that people get tested ten years before, at age 55, when the onset of Alzheimer's would typically begin. If they exhibit elevated Abeta 42levels then, that is the time to begin taking daily ibuprofen to ward off the disease. 

Unfortunately, most clinical trials to date have focused on patients whose cognitive deficits are already mild to severe, and when the therapeutic opportunities in this late stage of the disease are minimal. Consequently, every therapeutic trial has failed to arrest the disease's progression. Their discovery is a game changer. They now have a simple test that can indicate if a person is fated to develop Alzheimer's disease long before it begins to develop. Individuals can prevent that from happening through a simple solution that requires no prescription or visit to a doctor. This is a true breakthrough since it points in a direction where AD can eventually be eliminated. 

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Well, that wraps up another episode of Biotechnology Focus radio! Thanks for listening! If you have any questions or comments, please reach out to us at [email protected]. Tune in next week! From my desk to yours – this is Michelle Currie.  

Welcome to another episode of Biotechnology Focus radio – I am your host Michelle Currie. This week I will share with you an interesting article that I came across and then we will move on to the foremost part of the episode with Vatche Bartekian, here to tell us about his upcoming conference.   

It was a work in progress, but after eight long years neuroscientists at the University of Montreal discovered a molecular mechanism that helps make sense of how Lou Gehrig's disease, or amyotrophic lateral sclerosis (ALS), works. 

This discovery could lead to a valuable new treatment in the fight to cure this crippling disease. 

Amyotrophic Lateral Sclerosis is a disease that gradually paralyzes people because the brain is no longer able to communicate with the muscles of the body that we are typically able to move at will. Over time, as the muscles of the body break down, someone living with ALS will lose the ability to walk, talk, eat, swallow, and eventually breathe. 

While studies such as this do not immediately give rise to new treatments for people living with ALS, they do deepen our understanding of the disease. ALS is very complicated; many cellular functions get mis-regulated. This type of work provides important information for future drug targets and the development of biomarkers aimed at detecting the disease more rapidly and following its progression. 

The research began eight years ago when Jade Emmanuelle Deshaies, a research associate in neurosciences at the u of m and her supervisor, associate professor of neurosciences Christine Vande Velde, started investigating what happens to various molecules when TDP-43, a protein that binds the 'messengers' in the cell known collectively as RNA and that is central to ALS pathology, is removed from the nucleus. 

In molecular biology, genes encode RNA and the RNA then gets translated into proteins. There are many different versions of RNA, each encoding many different versions of a protein. TDP-43, for one, binds RNA and can change how it is spliced – in a sequence of ABCD, for example, or of ABCEFG – a process called alternative splicing. Another RNA binding protein is hnRNP A1, and it gets spliced into two variants, both regulated by TDP-43. This is important because TDP-43 is known to be a major component of non-living substances in the cell called cytoplasmic inclusions that are seen in over 97 per cent of ALS cases. 

The data they have show that when TDP-43 is either not there at all, or is just absent from the nucleus, you can change the splicing pattern of hnRNP A1. The big picture is that there is a much more broad spectrum of RNA metabolism mis-regulation than what was previously thought. And with that, there is more understanding of what's going wrong, and given this new knowledge, they can potentially develop a therapy that targets this mechanism. 

There is also development that parallels this research in spinal muscular atrophy (SMA) – another motor neuron disease. Scientists know that hnRNP A1 plays a role in its progress, controlling the splicing of an important gene called SMN, survival motor neuron. Vande Velde and her team don't yet know whether or not the new splice variant they discovered changes SMN levels or function, but they point to a new drug therapy announced last year for SMA that does target the splicing of SMN by hnRNP A1. 

The most amount of ALS research is done in Quebec than any other province. As Deshaies sums it up, "Science is rarely straightforward. It often takes a winding road before leading to explanations and true understanding of what we observe." 

Well that wraps up another episode of Biotechnology Focus radio. I want to thank  Vatche Bartekian again for discussing his upcoming conference with us, and thank you all for listening! From my desk to yours – this is Michelle Currie.  

Welcome to another episode of Biotechnology Focus radio! I am your host, Michelle Currie, here to give you the rundown on Canada's biotech scene. This week we have stories about a possible Ebola treatment, how there may be a link between an increase in cholinergic system activity and parkinson's disease, CRISPR makes its move on RNA, and according to a u of t study, rheumatoid arthritis patients have a higher risk of earlier mortality. So, keep listening to hear what's going on from coast to coast!

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In the wake of the 2014 Ebola outbreak, with more than 11,000 known deaths, researchers are attempting to come up with innovative ways to prevent and cure the disease. Due to the dire nature of the virus, it sheds light on the limitations of the medication currently in circulation.

Now, University of Guelph researchers have shown that an innovative antibody delivery method could offer an effective way to prevent and treat Ebola infection.

Their goal is to make an antibody-based therapy that can protect against all strains of Ebola, and potentially the Marburg virus as well. It would be used to stop the spread of the virus in outbreak situations.

The researchers say monoclonal antibody therapies (mAbs) hold promise for the treatment of the Ebola virus, but monoclonal antibody therapies are a costly operation and provide only short-term immunity. That could change though thanks to a recent discovery by lead researchers Sarah Wootton and Laura van Lieshout. Their findings were published in the Journal of Infectious Diseases.

The approach technique that the researchers are using has been seen in studies with the human immunodeficiency virus (HIV). It delivers a monoclonal antibody gene through a viral vector to bypass the need to generate a natural immune response – something that can take the body weeks to occur and quite frankly, time is of the essence with this particular disease.

Wootton found that using the adeno-associated virus (AAV) to deliver antibodies was remarkably effective at keeping the Ebola virus infection at bay in mice. Other researchers have used the adeno-associated virus extensively to treat a variety of genetic disorders.

The goal is to use the adeno-associated virus gene therapy vector to deliver the DNA blueprint to a cell, and that cell will produce a protective antibody against the Ebola virus, which is then secreted into the bloodstream and protects mice from infection.

The approach provided 100 per cent protection against an Ebola infection in mice using two separate types of monoclonal antibodies, and 83 per cent protection with a third. A "cocktail" of two antibodies provided sustained protection against Ebola for up to five months.

Once the antibody gene is delivered, antibodies will be continually reproduced in the bloodstream. Mice in the laboratory expressed the antibody for more than 300 days.

Researchers are hoping to utilize this technology in a post-exposure scenario.

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There is a particular gene mutation that happens in the brain that could be linked to an inherited form of Parkinson's disease (PD) that might shed some light on a controversial theory about where PD begins in the brain.

Idiopathic PD, a sporadic form of the disease, affects the dopamine system and is treated with replacement therapy to restore the brain's natural chemical balance and alleviate physical symptoms. Frequently, other neurotransmitter systems are involved, but it is not yet clear whether this happens pre- or post the dopamine loss characteristic. By studying people with the inherited form of the disease, researchers hope that they will be able to determine brain involvement prior to the development of symptoms.

The results of an international collaboration, led by Dr. Jon Stoessl, published in The Lancet Neurology shows that mutations in the LRRK2 – a gene associated with an inherited form of PD – can cause imbalances in the cholinergic system of the brain, but not in the way they thought. The cholinergic system is responsible for learning and memory. An imbalanced cholinergic system has been witnessed in other neurodegenerative disorders, including Alzheimer's.

While the investigators expected to find evidence of reduced cholinergic activity in the brain, positron emission tomography (PET) scans revealed widespread increases not only in people with the LRRK2 mutation-related form of PD, but also in unaffected individuals who carry the mutation but do not yet have manifestations of disease. Changes in the cholinergic system are thought to contribute to PD complications including cognitive difficulties, postural instability and sleep disturbances.

It is possible that an increase in activity may reflect the brain's attempt to compensate for dysfunction related to the mutated gene, and may also explain why patients with LRRK2 mutations have fewer problems with certain complications of disease, even though their PD is in most ways similar to the usual sporadic form of the disease. This provides a tremendous opportunity to study people with Parkinson-causing genetic mutations before they develop.

The findings of this study have considerable implications for understanding how the disease begins to manifest in the years before diagnosis, and builds on research previously published last year that demonstrated that patients with the LRRK2 mutation show an increase in serotonin nerve terminals before a formal Parkinson's Disease diagnosis, possibly reflecting the brain's attempts to compensate for the decrease in dopamine associated with onset of physical symptoms.

According to Statistics Canada, PD is the second most common neurodegenerative disease in Canada with an estimated 55,000 people suffering from it. It is a progressive disorder of the nervous system that affects movement. It develops gradually, sometimes starting with a barely noticeable tremor in just one hand. But while a tremor may be the most well-known sign of Parkinson's disease, the disorder also commonly causes stiffness or slowing of movement that worsens as it progresses. The majority of new diagnoses are in adults over the age of 64.

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CRISPR/Cas9, the "scissors" of life sciences, is now not only targeting DNA, but RNA as well.

Scientists from the Salk Institute in the U.S. have created this new tool, CasRx, to correct protein imbalances in cells. This provides researchers with a powerful way to develop new gene therapies, as well as investigate fundamental biological functions.

Bioengineers are like nature's detectives, searching for clues in patterns of DNA to help solve the mysteries of genetic diseases. CRISPR has revolutionized genome engineering, and the researchers wanted to expand the toolbox from DNA to RNA.

CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea (the domain of single-celled microorganisms). These organisms use CRISPR-derived RNA and various Cas proteins, including Cas9, to foil attacks by viruses and other foreign bodies. They do so primarily by chopping up and destroying the DNA of a foreign invader. When these components are transferred into other, more complex, organisms, it allows for the manipulation of genes, or "editing."

The Salk team decided to search bacterial genomes for new CRISPR enzymes that could target RNA, which could then be engineered to address problems with RNA and resulting proteins.

A given RNA message, for example, can be expressed at varying levels and its balance relative to other RNAs is critical for healthy function. Furthermore, RNA can be spliced in various ways to make different proteins, but problems with splicing can lead to diseases such as spinal muscular atrophy, atypical cystic fibrosis and frontotemporal dementia (FTD). So, a drug that targets toxic RNAs or RNAs resulting from improper splicing could have a life-changing impact for people with these types of devastating diseases.

The researchers began the project with the hypothesis that different CRISPR systems may have been specialized throughout an evolutionary arms race between bacteria and their viruses, potentially giving them the ability to target viral RNA.

They developed a computational program to search bacterial DNA databases for particular repeating DNA sequences. Whilst this was happening, they discovered a family of CRISPR enzymes that targets RNA. They called it Cas13.

The name is derived from the gut bacterium Ruminococcus flaveflacians XPD3002 due to it being the best version for use in human cells, because just like Cas9, Cas13 enzymes originate from different bacterial species and vary in activity.

The scientists tried out this new method in a dementia patient, attempting to replace the damaged cells with healthy ones. CasRx was 80 per cent effective. The team genetically engineered CasRx to target RNA sequences for the version of the tau protein that is overabundant. They did this by packaging CasRx into a virus and delivering it to neurons grown from a frontotemporal degeneration patient's stem cells.

Compared to other technologies that target RNA, CasRx is unique due to its small size – making it easier to package into therapeutically relevant viral vectors – its high degree of effectiveness, and that it creates no discernible off-target effects compared to RNA interference. The Salk team is excited about the possibilities their tool opens up for exploring new biological questions about RNA and protein function, as well as therapies to tackle RNA and protein-based diseases.

To quote one of the authors of the study, "Nature is full of so many secrets. It's really a rich, untapped resource for inventing new technologies."

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According to a study done by the University of Toronto, sufferers of rheumatoid arthritis are more likely to have further complications and die at a younger age than the general population. The study was examining causes of death of Ontarians over a 14-year period.

Everyone deserves to live the same length and quality of life. Mortality is also one of the strongest markers to evaluate inadequate care. The excess mortality related to rheumatoid arthritis that the researchers observed may suggest inadequate attention to control of the disease and its related morbidity.

The study is one of the largest of its kind to comprehensively look at causes of death over an extended period. More than 87,000 patients with rheumatoid arthritis in Ontario were included in the study and compared with more than 340,000 members of the general population over a span of 14 years.

Causes of death were found to be quite similar between the general population and those with rheumatoid arthritis, but the notable difference was that those with the disease were dying at a much younger age – which is something that concerns the researchers.

Rheumatoid arthritis is a chronic condition that can affect two to three per cent of older adults. As an inflammatory disease, rheumatoid arthritis can affect more than just the joints in the body – ongoing inflammation often leads to further complications and multimorbidity in patients. This means that individuals will likely have multiple chronic conditions occurring simultaneously, such as diabetes and high blood pressure, or heart disease and a respiratory illness.

The study also found that among arthritis sufferers, one in three were dying of complications attributed to heart disease. The head researcher wants to underscore the importance of improving preventative measures to slow down the progression of some of these co-morbid conditions in order to improve a patients' overall life expectancy.

The hope through this research is that it will shed light and awareness on the disease and inspire patients to play a more active and vigilant role when it comes to their health.

The study was published in Arthritis Care & Research and was supported by the Catherine and Fredrik Eaton Charitable Foundation, the Canadian Institutes of Health Research, and the Arthritis Society Post Doctoral Fellowship.

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Well, that wraps up another episode of Biotechnology Focus radio! I hope you enjoyed it! Next week I'll have Vatche Bartekian on the show to tell me about his event coming up in May! Stay tuned and have a great week! From my desk to yours – this is Michelle Currie.

082 | Discoveries: contending with the superbugs 

Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on what's happening on the Canadian biotech scene. This week there have been some novel research discoveries that McMaster University, The University of Alberta, The University of British Columbia, The University of Waterloo and The University of Manitoba have been pumping out that I would like to share with you. So, keep listening and find out what exciting stories are happening from coast to coast!  

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Researchers from McMaster University have pinpointed a gene that is the culprit for neurological disorders, including autism. 

They found that modifications of the gene thousand and one amino-acid kinase 2, aka TAOK2, has a direct link to these disorders. This gene encodes a serine/threonine protein kinase that is involved in many different processes, including, cell signaling, microtubule organization and stability, and apoptosis. This is the first comprehensive study that supports previous research suggesting the involvement of this gene and is published in Molecular Psychiatry. 

According to Karun Singh, study co-author and researcher with McMaster's Stem Cell and Cancer Research Institute, "Our studies reveal that in complex brain disorders that have a loss of many genes, a single deleted gene is sufficient to cause symptoms for the patients. This is exciting because it focuses our research effort on the individual gene, saving time and money as it will speed up the development of targeted therapeutics to this gene alone." 

Many neurodevelopmental disorders are caused by large missing pieces of genetic material in a person's genome that contain several genes, termed a 'microdeletion'. Accurately diagnosing a gene microdeletion helps doctors to predict patient outcome and to determine if a new treatment is available. 

The researchers used genetically engineered models and computer algorithms to study a human genome, which allowed them to pinpoint the single gene in question. 

The next step will be to screen candidate drugs that correct the cognitive brain deficits cause by genetic mutations in TAOK2, and identify candidates for pilot clinical trials. 

The paper complements a study led by Singh on gene microdeletion published in American Journal of Human Genetics in early February. 

The research was led by Singh in collaboration with Stephen Scherer from the Hospital for Sick Children. Additional researchers came from McMaster University, the Hospital for Sick Children, University of Toronto, the University Medical Center Hamburg-Eppendorf in Germany, Assiut University in Egypt and the University of Helsinki in Finland. 

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There was a time when the thought of growing a human body part in a lab would have been outrageous. These days, those once incredulous thoughts have become a reality. 

Now, the researchers from the University of Alberta have found a way to grow human nose cartilage that will be safer and more accessible to use for facial reconstruction surgeons and will mean fewer surgeries and less pain for patients. 

The team conducting the research project used a clinically approved collagen biomaterial as a scaffold to grow new cartilage that they can harvest and shape for patients who need nasal reconstruction. 

The vision is that the surgeon would simply take a small biopsy of cartilage from inside the nose and provide it to the lab. The lab would then manufacture the cartilage for the surgeon in the appropriate shape and size. Once it has finished growing, the surgeon would then take that cartilage and insert it into the patient's nose at the time of the operation. 

Nasal reconstruction is a relatively common surgical outcome resulting from skin cancer. In 2015, there were more than three million cases of skin cancer in North America alone. About one-third of cases occur on a patient's nose, with treatment options often leading to loss of function and disfigurement. 

This typically ends up being a very traumatic event for the patient and comes with a high pathological cost. They really can't hide these defects – they are very obvious. Often these patients will not interact socially because they are embarrassed by their appearance. So, the ability to help reconstruct a patient's nose is really important. 

With the assistance of six cartilage donors, the researchers harvested the cartilage cells – known as nasal chondrocytes – and multiplied them in a lab. They then seeded the cells in a scaffold to grow new tissue in a bioreactor. It takes roughly six weeks to grow enough cartilage for nasal reconstruction. 

This engineered cartilage minimizes other risks and is deemed to be a superior method than that of the cartilage harvesting from the rib or ear. Cartilage taken from the rib carries a greater chance of infection, potentially collapsing the lung and an unnecessary surgery that will take the patient a longer to recuperate. Rib cartilage can also undergo warping after nasal reconstruction surgery, meaning it may not maintain the shape the surgeon wants it to. Cartilage taken from the ear is also challenging in that it can become brittle and difficult for the surgeon to manipulate. Engineered cartilage eliminates those deficiencies and could potentially supply unlimited quantities for surgeons. The University of Alberta team says it can also be custom-made for the patient. 

An associate professor of surgery at the University of Alberta describes it as kind of like when you go to the tailor to get your suit made. They measure the patient based on the digital scans, and then basically just populate the cells. 

The researchers have yet to test their high-quality engineered nasal cartilage in human patients. They hope that within the next two years they can begin clinical trials to prove the efficacy of the cartilage in the operating room. 

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Recent research conducted by the University of British Columbia (UBC)and BC Cancer denotes that precancerous lesions in the mouths of non-smokers are more likely to evolve into cancer than smokers. 

Even though smoking unequivocally is related to mouth cancers, UBC dentistry PhD candidate Leigha Rock found that precancerous lesions in non-smokers are more than twice as likely to progress to cancer at an even faster rate than a smoking-associated counterpart. The study was published in Oral Oncology. 

This is the first published study where the main focus was to examine the difference in risk of progression to oral cancer between non-smokers and smokers with oral precancerous lesions. While other studies have also reported a higher rate of transformation among non-smokers, this study looked at multiple risk factors including genetic markers. 

Rock and colleagues looked at the case history of 445 patients with oral epithelial dysplasia (OED), a type of precancerous oral lesion, enrolled in the B.C. Oral Cancer Prediction Longitudinal study. One-third of the patients were non-smokers. 

Amongst the researchers' findings were that lesions on the floor of the mouth in non-smokers were 38 times more likely to progress to cancer than in smokers. This study is the first to report a quicker progression to cancer in non-smokers indicated at three-year and five-year rates of progression, and at 7 and 6.5 per cent higher than smokers, respectively. 

The researchers suggest that the main difference in outcomes is due to a variance in the root causes of the lesions. In smokers, the oral epithelial dysplasia OED is likely the result of environmental factors. Whereas, in non-smokers, genetic susceptibility or mutations are likely to blame. 

The findings show that molecular genomic markers can identify high-risk lesions, regardless of risky habits like smoking, and should be an important consideration in patient management. 

The study's results also stress the importance of taking oral lesions seriously, especially when they occur in non-smokers: "If you see a lesion in a smoker, be worried. If you see a lesion in a non-smoker, be very worried. Don't assume it can't be cancer because they're a non-smoker; research indicates non-smokers may be at higher risk." 

This research was funded by the BC Cancer Foundation, the National Institutes of Health, and the National Institute of Dental and Craniofacial Research. 

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And some very exciting news, especially in this age of antimicrobial resistance, scientists from the University of Waterloo and the University of Manitoba have developed a new therapy to combat deadly bacteria that infects patients worldwide. 

The new therapy is a biocide that targets an antibiotic-defiant bacterium such as Methicillin-resistant strafill cock us  are e us  (Staphylococcus aureus) (MRSA) to combat superbugs. 

Professors at the University of Waterloo wanted to be able to help vulnerable patients suffering from chronic infections. Because once a patient is infected with a resistant strain of bacteria it is very difficult to get them well again. 

This latest development provides hope in an age where bacteria are becoming resistant to antibiotics faster than researchers can develop new ones. The World Health Organization estimates 700,000 people die annually from antibiotic-resistant infections and they expect this toll to climb to 10 million by 2050, higher than the current death rate from cancer and even motor accidents combined.  

University of Manitoba researcher, Song Liu, created a potent biocide that kills all bacterial cells – even the antibiotic-resistant ones. The biocide was limited to surface wounds due to its poor selectivity between bacterial and mammalian cells, but if they could deliver the biocide to a target inside the body, it would kill even the most resistant superbug. 

Accompanying Liu's work, Ho encased the biocide in solid-lipid nanoparticles and then added an antibody – a protein that would seek out Methicillin-resistant strafill cock us are e us bacteria over other cells. When the solid-lipid nanoparticles reach the bacteria, they release the biocide, killing the target but leaving healthy cells unaffected. The optimal outcome. 

The results from the initial experiments appear to be quite promising. Still, there is a lot of work to do before this is available as an alternative to antibiotics. The next step is to find out whether the biocide gets released outside or inside the cell according to the researchers.  

The researchers also believe that antimicrobial resistance will be unlikely to happen with their solid-lipid nanoparticles because the antibodies that are being used to target Methicillin-resistant strafill cock us are e us won't cause the bacteria to develop an enzyme or other defence mechanisms in response. 

This therapy offers a new line of defence in this critical time to confidently outpace antibiotic resistance. 

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Well, that's it for this week's episode of Biotechnology Focus radio. Perhaps next week there will be more riveting news from these universities and more from others I am sure. Modern medicine is advancing at such a pace, it's hard to keep up! Be sure to check our website for the full stories and get your fill daily of what's happening on the Canadian biotech scene at www.biotechnologyfocus.ca. Thanks so much for listening in! Hope you have a great week ahead. From my desk to yours – this is Michelle Currie.  

Welcome to another episode of Biotechnology Focus radio. I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene. This week I'll be discussing how the regenerative medicine community is abuzz, expanding personalized medicine, and the very recent announcement from the Ontario government that brings great news to the life sciences sector.  

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The regenerative medicine field, which includes cell and gene therapies (CGTs), is still abuzz with the fall approvals of three CGTs by the U.S. Food and Drug Administration: Novartis' Kymriah, Gilead/Kite Pharma's Yescarta and Spark Therapeutics Inc.'s Luxturna. 

At the Cell and Gene Therapy World conference in Miami, Florida (January 22-25), many of the talks were either about the approved treatments or congratulating the industry on these significant milestones. 

Reni Benjamin, of Raymond James Financial, reminded delegates that the pharmaceutical industry is also feeling confident about cell and gene therapes s. Acquisitions in 2017 were worth billions: Gilead acquired Kite for $11.9 billion, Takeda bought Ariad for $5.2 billion and Roche acquired Ignyta for $1.7 billion. As the conference was just getting underway, the news was announced that Celgene is buying Juno Therapeutics for $9 billion. 

Illustrating the future of the field are the more than 1,300 currently open clinical trials listing stem cells (from sources other than blood) as the primary therapeutic, the 1,000 clinical trials in gene therapy, and clinical trials involving chimeric antigen receptor (CAR) T cells (a type of immune system cell) accounted for around half of clinical trials in 20162. 

As such, global investment in the cell and gene therapies and regenerative medicine industry is booming. For example, public and private investment in immuno-oncology has grown to $1.5 billion2. When it comes to gene therapies, the forecast for the year 2025 ranges from $4.3 billion to $10 billion2 due to recent advances in the understanding of genetic disease, and innovation in genetic engineering tools. Altogether, it is estimated that the regenerative medicine industry will explode to a valuation of up to $20 billion by the year 2025. 

So, where does Canada sit in terms of being an innovator in these advanced therapeutic technologies? 

Let's start with the good news. Canada is a prominent force in this emerging global field. We have a strong backbone of Canada-based researchers who are recognized scientific leaders, and a robust system for the development of highly-qualified personnel through Canada's universities. We have also benefited from strategic investments in research, collaborative networks and infrastructure, and are developing a deep understanding of how to translate these advanced therapies from the bench to the bedside. 

One way to sustain Canada's leadership position is to nurture the right skills and education within our borders. Encouraging STEM (science, technology, engineering and mathematics) education from a young age is a necessary first step. Extending STEM-based education with biomedical engineering programs at the university level is a good strategy for supporting the growth of Canada's CGT and regenerative medicine industry. Biomedical engineering – where engineering design principles and mathematics are applied to medicine and biology, allowing students to make significant contributions to improving human health by finding new diagnostic or therapeutic solutions – is an area Canadian universities are increasingly focusing on. 

An illustration of how biomedical engineers are already impacting the regenerative medicine field can be found at the University of Toronto's Institute of Biomaterials and Biomedical Engineering (IBBME) and at Medicine by Design. The 55-year-old IBBME fosters a multidisciplinary research community where students and investigators in engineering, medicine and dentistry collaborate to develop innovative solutions that address global challenges in human health. Their impact can be seen in the development of breakthrough biomedical devices and new biomaterial products. 

Funded in 2015 with a generous federal grant, Medicine by Design builds on IBBME's successful multidisciplinary model to conceive, create and test strategies to address critical problems in regenerative medicine. By working across disciplines and generating and using emerging methods, like genome editing, computational modelling and synthetic biology, Medicine by Design is generating a deeper understanding of core biological concepts controlling stem cell fate, and devising new therapeutic approaches that will improve health outcomes. 

This successful approach is now receiving a significant boost in Vancouver, where the University of British Columbia (UBC) has launched a new School of Biomedical Engineering as a partnership between the Faculty of Medicine and the Faculty of Applied Science. 

Centre of commercialization and regenerative medicine, a Toronto-based leader in developing and commercializing regenerative medicine technologies, understands how the intersection of engineering and medicine, introduced by biomedical engineers, can help provide the tools that will advance the industry now and into the future. 

One area where Centre of commercialization and regenerative medicine employs biomedical engineers is in its Centre for Advanced Therapeutic Cell Technologies (CATCT), a joint investment by GE Healthcare and the Government of Canada. Biomedical engineers work on process development strategies and solutions, and on projects involving reprogramming and engineering cells, immunotherapies and gene therapies. Operational for over a year, Centre for Advanced Therapeutic Cell Technologies was created to accelerate the development and adoption of cell manufacturing technologies that improve patient access to novel regenerative medicine-based therapies. The team introduces new technologies to solve emerging technical challenges and closes gaps in current and future workflows. 

Our next challenge is to make certain that we have the people, technologies, processes and infrastructure to ensure Canadians have equitable access to these potentially game-changing therapies. Biomedical engineering programs are a start. Engineers are trained to look for efficiencies through cost reductions and improved technologies. 

We need to build a Canadian innovation cluster that will attract talent and business expertise to capture the intellectual property developed in Canada and mobilize it for the benefit of Canadians. 

We also need to work with government to position our health-care system as part of our competitive advantage. A big part of getting to this step in getting to this solution is starting to look at health economic models that integrate therapeutic costs and savings from development through to long term patent treatment costs. 

Together, Canada's companies, networks, researchers, start-ups and innovative centres are starting to deliver on the promise of regenerative medicine. With the technical know-how and a spirit of collaboration, biomedical engineers are a driving force in the country's quest to lead the regenerative medicine industry into the future. 

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Personalized medicine is becoming a very popular term heard amongst researchers and the scientific community. It is a more tailored approach to preventing disease that is based on an individual's predispositions. Whichever way you put it – personalized medicine, genomic medicine, precision medicine – it is reshaping healthcare. 

Dr. Richard Kim, a scientist at Lawson Health Research Institute and clinical pharmacologist at London Health Sciences Centre (LHSC), has received $4.4 million to study an expanded personalized medicine program at London Health Sciences Centre. One-third of the funding comes from the provincial government's Ontario Research Fund (ORF) while the remainder is contributions from Thermo Fisher Scientific and donor funding through London Health Sciences Foundation. 

Personalized medicine uses pharmacogenomics – the study of genetic changes that alter the way a person responds to individual drugs. The new funding will enable researchers to follow patient outcomes and assess the cost-effectiveness of London Health Sciences Centre's personalized medicine program, providing evidence on the relationship between the cost of the program and how patient care is improved. 

London Health Sciences Centre's personalized medicine program involves the full integration of research into patient care and was the first in Canada to implement personalized medicine as a clinical strategy. The practice began in 2008 through Dr. Kim's research on warfarin – a blood thinner prescribed to treat blood clots. 

Adverse drug reactions in patients is a significant problem. Some drugs do not metabolize with every patient, and can even lead to toxicity. It is the fourth leading cause of death among hospitalized patients and costs the Canadian health care system over $5 billion a year. 

Dr. Kim explains, "For every medication, there are patients who should be prescribed lower or higher than the recommended standard dose and patients who should be prescribed an entirely different medication. Personalized medicine studies a patient's unique DNA to ensure he or she is prescribed the right dose of the right medication at the right time." 

The team's research continues to grow since inception and is providing testing for several other drugs. For example, they can now offer testing for cancer patients that have been prescribed 5-fluorouracil – a highly toxic form of chemotherapy – but is integral in treating bowel, stomach, head, and neck cancers. 

Oncologists at London Health Sciences Centre's London Regional Cancer Program can now refer patients to get tested for their potential reaction to 5-fluorouracil to better predict if they may or may not have an adverse reaction. A blood sample will be taken and tested with genotyping, and a full report given to the recommending oncologist. If a patient's predicted to react poorly with the drug, they can follow clinical guidelines to either reduce the dose or find a method of treatment. 

The team will study the outcomes of any patients referred to the program, including hospital stays, emergency department visits, and physician visits. These patients will be compared to others in the province using provincial health care data from the Institute for Clinical Evaluative Sciences (ICES). The team hopes to demonstrate the cost-effectiveness of implementing personalized medicine in a large acute-care hospital in Ontario. 

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The most recent announcement from the government of Ontario this past week was that it is investing $50 million in venture capital funds focused on life sciences. 

Ontario is moving forward with their plan for a venture capital fund to aid life sciences firms access the capital they need to grow their business, create jobs, and grow on a global level. 

The Ontario Capital Growth Corporation (OCGC) would like to identify fund managers to partner with other institutional investors such as corporations, banks and pension funds. Ontario's new life sciences venture capital fund is designed to respond to the challenges faced in raising capital by innovative, high-potential life sciences companies to scale up and reach global markets. 

The Hon. Reza Moridi, Minister of Research and Innovation says, "Providing much needed capital to growing life sciences companies is a crucial step towards a strong and sustainable life sciences ecosystem. Supporting high-potential life sciences companies will create good jobs and help commercialize technologies and services for improved healthcare at home and around the world." 

Ontario's new venture capital fund focused on life sciences is designed to respond to the challenges faced in raising capital by innovative, high-potential life sciences companies to scale up and reach global markets. It will also help businesses foster new discoveries, including new technologies, treatments and cures for illnesses while supporting high quality, knowledge-based jobs for people across the province. It will also drive Ontario's ability to attract and retain talent. 

The Ontario Capital Growth Corporation, venture capital agency of the government of Ontario, was created to promote and develop the venture capital sector in Ontario, so that more high-potential technology companies have access to the capital needed to grow and prosper. 

Supporting innovation in the life sciences is part of Ontario's plan to create fairness and opportunity during this period of rapid economic change. The plan includes a higher minimum wage and better working conditions, free tuition for hundreds of thousands of students, easier access to affordable child care, and free prescription drugs for everyone under 25 through the biggest expansion of medicare in a generation. 

Ontario is the largest life sciences jurisdiction in Canada with more than 50 per cent of overall Canadian revenue. The province includes an incredible 1,840 firms employing close to 61,000 people across the province. This fund will open many doorways for Canadians and Ontarians.  

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Well, that wraps up another episode of Biotechnology Focus radio. I hope you enjoyed it. If you have a story idea or would like to be on the show, please email me at [email protected]. To see the articles in full check out the website biotechnologyfocus.ca ca so you don't miss a beat! Have a momentous week. From my desk to yours – this is Michelle Currie.

080 | Pursuing cures and advancing innovation  

Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on what's been happening on Canada's biotech scene. It has been a busy last couple of weeks as the new genomics cloud platform was launched, a researcher from Roche Canada shares her input on future of innovation in cancer care, and the fight against cancer innovation trust invests almost half a mil in Ontario research technologies.  

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The world is opening up to the idea of genome sequencing. What was once a far-fetched idea is now beginning to materialize – and we are only at the tip of the iceberg. Information technology like Facebook, Google, Wikipedia and Uber are all prime examples of impactful software platforms that connect people with data that have set the stage for the next act. 

When you look at where DNA sequencing began back in the 1970's with the "Sanger sequencing method" as a process of determining the order of bases in the length of DNA, we've come a long way. But still, researchers are at the forefront of this revolution of gathering our personalized genetic information and using it to power the next generation of safer and more effective "precision" medicines. 

This is where Marc Fiume and his team from DNAstack, a Toronto-based cloud genomics company, have their role to play. Started in 2014, the company began work with some exciting researchers from around Canada whose hot topics included autism and cancer research. But constantly they were told that the researchers just didn't have enough samples to make sense of all the data they were collecting and that they really needed a platform that would connect them with other researchers globally who found themselves in the same position. Inspired by the concept of Facebook, they decided to build their own platform where genetic research could transpire among researchers worldwide. 

He refers to the lack of data access as "potentially keeping life-saving information in a basement server room" and is one of his biggest frustrations when it comes to genomic research. Unveiling the sequence of a genome is challenging, time-consuming and expensive. Perhaps that is the reason why such a platform can no longer be just a notion, but become a mandatory tool so we can further our knowledge unified, instead of trying to connect the dots apart. 

Genome sequencing is a lot like "decoding" of a foreign script or ciphering out a code of each individual's personal genome. It is a long string of letters that forms a sort of molecular blueprint that is unique for each of us. These "strings" of letters are about six billion long, and currently, researchers are only grasping about a very small per cent of what those letters represent. This is why the need for sharing information should be a necessity. 

In an attempt to break this societal self-inflicted mold, Marc worked with Dr. Stephen Scherer from The Centre of Applied Genomics on the "Personal Genome Project Canada" to facilitate the publication of health and genome records online for free. The intention being that whether you are sick or healthy, it is incredibly useful personally and for the research community to have your genome sequenced. Perhaps you have a predisposition to a potentially harmful genetic disease that you were not aware of before and could catch it before it starts, or if you are a carrier, or if you simply want to learn more about your ancestry. All of this is possible with genome sequencing. While some may not be ready to have theirs published online, it could still be made available to you in the privacy of your own home. 

Marc and Ryan Cook, the other co-founder of DNAstack, have both tried to decrease the unease attached to publicly airing one's genome sequence by publishing their own. "It's about empowering and making key decisions about their healthcare in a way that's not scary and also to break down barriers about data sharing," comments Marc. 

There are now 56 genome researchers that are bearing it all for the world to see, and encouragingly are following up on some of the data that they have found. 

DNAstack recently launched their Canadian Genomics Cloud platform that is designed to better connect data, researchers and systems across the country to accelerate genomic discoveries and the implementation of precision medicine. It was invented by Canadian leaders with decades of experience in genomics, sequencing, cloud computing, software, security, and policy to democratize access to best-in-class infrastructure while respecting the unique national and provincial requirements for data privacy and security. Their aim is to service the needs of Canadian genome scientists from research institutions, clinical laboratories, pharmaceutical companies, hospitals, and industry. 

The hope is to demonstrate that Canada now does have the capacity to do a precision medicine initiative at scale. Canada is really ready for this." – says Marc.  

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For most of us, the start of a new year is a natural time to reflect on our progress as individuals. We take stock of the lives we've lived, the advances we've made, the impact we've had on those around us and the steps we need to take in the year ahead to achieve our goals.  

For the Pharmaceutical and Biotechnology industry, the start of the new year is much the same. Standing at the doorstep of 2018, many of us who have spent our lives trying to advance healthcare around the globe believe that we are at a point in our careers, where science is progressing at a rapid rate. 

In fact, some of us would venture that science is progressing at a rate that is outpacing our ability – as healthcare providers, as governments, as payers and as hospital institutions – to integrate these cutting-edge advances into clinical practice. While this reality poses significant challenges, it's exciting to be on the threshold of so many unprecedented discoveries and novel treatment approaches for some of the world's most devastating diseases. 

The field of biotechnology is rich with discoveries that will have a dramatic impact on Canadians in 2018 and beyond. However, there are three key developments in the area of oncology in which we can expect to see some of the most transformative and immediate changes. These include: 

the expanded role of diagnostics to optimize treatment choice; 

the adoption of histology-agnostic treatment approaches; and 

the next phase of true precision medicine 

Expanded Role of Diagnostics 

In recent years, the use of diagnostic tests within the Canadian cancer care setting has become an increasingly important practice, particularly for guiding treatment decisions and optimizing the patient's chances for positive outcomes. In fact, it's estimated that nearly 70 per cent of all treatment decisions today involve a pathology and/or laboratory investigation. 

While the role of predictive biomarker testing has already been well established for some time in certain tumour types (such as HER2 in breast cancer or EGFR and ALK in lung cancer) we are witnessing the emergence of two trends that could further enhance patients' care and their experience with our healthcare system. These include the ability to simultaneously look beyond a single biomarker through genomic profiling, and the viability of liquid/blood-based biomarker testing. 

In 2018 we can expect to see a continued shift among healthcare providers to rely more on comprehensive genomic profiling to map each patient's unique genomic profile to identify alterations across hundreds of genes known to be relevant in the development and progression of cancer. This broad approach optimizes the use of the available tumour tissue and provides physicians with the most comprehensive information to help guide their treatment selection. There is particular value in this approach for patients who have exhausted all standard treatment options or for those with rare forms of cancer with limited known effective treatment options. 

Canadian institutions, like the British Columbia Cancer Agency, University Health Network in Toronto and The Jewish General Hospital in Montreal among many others, have already begun to demonstrate international leadership in this area with their in-house testing platforms and world-class genomic research programs. We are also seeing the emergence of third-party molecular information providers, such as Foundation Medicine Inc., an organization that has partnered with Roche to offer genomic tests to provide physicians with information about a tumour's unique genomic profile based on an interrogation of over 300 genes. These external services provide options for institutions that may not have the internal capabilities to offer such testing services and for patients who are looking for more comprehensive diagnostic information. All of these efforts are striving to rapidly expand treatment options by matching patients with approved targeted therapies, immunotherapies, and clinical trials based on their tumour's molecular profile. 

The second emerging trend in the space of predictive biomarkers is blood-based testing, which offers physicians a less-invasive testing mechanism for cases, in which there is insufficient tissue available for analysis. This may also prove to be a better option when a traditional tissue biopsy is not feasible due to tumour location, when a patient is in poor health, or when a physician and/or patient simply prefer a non-surgical option. In addition to supporting initial treatment choice, blood-based testing may also offer physicians the potential for continued monitoring in the future, resulting in earlier detection of disease progression and an assessment of resistance mutations to inform subsequent lines of therapy. 

A Change in Mindset 

Further to the evolution of diagnostic technologies, the increasing prevalence of targeted medicines is fundamentally challenging the way cancer research is conducted. We are no longer seeing only large randomized Phase III studies measuring overall survival for drug development, but more novel trial designs, including basket and umbrella studies, as well as smaller Phase II designs to measure the safety and efficacy of a drug. These new study approaches are aimed to accelerate scientific advancement and are addressing the challenges that exist when the prevalence of a particular molecular alteration is so limited that traditional trials seeking a large bolus of patients simply aren't feasible. 

In a basket trial, the impact of a single treatment across a spectrum of tumour types harbouring a particular alteration can be investigated. In contrast, umbrella trials inverse the approach, where multiple treatments are studied in patients with a common tumour type but who are stratified by molecular subtype. 

Close to home, the Canadian Profiling and Targeted Agent Utilization (CAPTUR) trial sponsored by the Canadian Clinical Trials Group in partnership with several pharmaceutical companies and academic institutions across the country is a combined basket/umbrella study enrolling patients of all cancer types who are stratified into different arms of the study to receive treatments based on the genomic profile of their tumours. Studies like CAPTUR will fundamentally shift how physicians view cancer, forcing them to look less at the type of cancer (e.g., breast, lung, colorectal) and focus on the molecular structure of the tumour. 

This histology-agnostic approach is one that is also gaining traction with regulatory authorities around the globe. In fact, the U.S. Food and Drug Administration (FDA) recently approved a PD-1 inhibitor to treat patients with any cancer type, provided their tumours were unresectable or metastatic and classified as microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR). This approval represented a significant departure from the traditional evidence requirements expected from a regulatory body and opens the door for further discussions and opportunities in other countries. 

The final development, which seems like a natural extension of our evolving mindset around the use of diagnostics and targeted medicines in oncology is our view regarding how medicines can be engineered to offer truly individualized treatments to patients. 

Though personalized medicines and immunotherapies are no longer considered 'new' in the rapidly evolving clinical landscape, the emergence of two types of truly bespoke cancer therapies marry these concepts to create what many consider a bold step in our quest to cure cancer. 

Recently, two chimeric antigen receptor (CAR) T-cell therapies were approved in the United States, ushering in the next wave of personalized cancer care. These therapies involve the genetic engineering and reinfusion of a patient's own T-cells to fight their unique cancers. While approved in specific hematologic cancers today, researchers are also exploring these therapies in many solid tumours and the hope remains that they will offer a whole new way to think of treatment in cancer. 

Still in its infancy, the second area of significant research is personalized cancer vaccines developed and manufactured for an individual patient based on the molecular profile of their tumours. Where off-the-shelf cancer vaccines have failed in the past, there is hope that these custom, uniquely tailored vaccines, in combination with checkpoint inhibitor therapies will succeed in transforming cancer care.  Close 

In closing, while it's easy to become discouraged by the often necessary hurdles required to integrate transformative products into current clinical practice, there has never been a more exciting time for those of who have built a career in the biotechnology industry; and there has never been a more exciting time for those of who have waited for a cure to cancer – a disease that has ravaged many of our families and has taken many of our friends and loved ones. 

The reality is that science will continue to outpace clinical practice. But the promise of these discoveries can be realized if we – as stakeholders within the healthcare system – are willing and open-minded to collaborate on solutions, especially as we look at the impact personalized medicines can have in therapeutic areas beyond oncology, offering meaningful solutions to an infinitely greater number of patients, enabling them to live longer, healthier lives. 

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The fight against cancer innovation trust announces four new recipients of funding through its prospects oncology investment competition. Those recipients are Dalriada Therapeutics Inc., 16-Bit Inc., a cancer biomarker study at the Ontario Institute for Cancer Research (OICR), and a virus-based therapeutic under development at the Ottawa Hospital and the University of Ottawa. FACIT's investments are imperative in bridging the capital gap often experienced by early-stage Ontario companies, helping corporations establish jobs and build roots in the province. The wide-ranging scope of the innovations, which span therapeutics, machine learning and biomarker development, reflect the rich talent pool within the Ontario oncology research community. 

Dalriada is a Canadian start-up founded with a mission to develop small molecule-based therapeutic technologies to battle diseases for which current treatment strategies are suboptimal or non-existent. With broad expertise in drug discovery, their efforts are currently centred on the preclinical development of a novel class (DT1) of small molecule inhibitors in cancers of the blood and brain as well as the development of a natural product for topical treatment of psoriasis and other inflammatory skin disorders. 

16-Bit, a start-up founded by two medical doctors from the University of Toronto's Diagnostic Radiology Program, is developing a machine learning algorithm to automate triaging of screening mammograms for breast cancer detection. Their focus is to utilize modern developments in machine intelligence to improve the accuracy, reliability, and speed of medical image interpretation while decreasing cost and barriers to healthcare. 

Diagnostics Development Program at OICR leader Dr. John Bartlett has developed a diagnostic gene test to predict which breast cancer patients can benefit from anthracycline chemotherapy and which patients can avoid the associated toxicity because the drug may not be effective against their cancer. 

The Ottawa Hospital and the University of Ottawa have developed a tumour-destroying virus based on the Vaccinia virus which adds a micro-RNA payload to enhance cell killing against pancreatic cancer. This targeted therapy is expected to be more precise and less toxic than conventional therapies for this difficult-to-treat tumour. 

The Prospects Oncology Fund delivers on FACIT and OICR's shared vision of advancing breakthrough innovations to the benefit of patients and Ontario's knowledge economy. Translating early-stage innovations and positioning them to raise additional funding supports Ontario's competitive position as a destination for biotechnology. 

Congratulations to all the strong applicants and in particular these outstanding awardees in their quest to make a difference for patients living with cancer. 

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Well, that wraps up another episode of Biotechnology Focus radio. I hope you enjoyed it. If you have a story idea or would like to be on the show, please email me at [email protected]. To see the articles in full check out the website biotechnologyfocus.ca and laboratoryfocus.ca so you don't miss a beat! Have a momentous week. From my desk to yours – this is Michelle Currie.  

079 | Acknowledging some of the industry's best

Welcome to another episode of Biotechnology Focus radio. I am your host, Michelle Currie, here to give you the lowdown on the Canadian biotech scene. Today, I will be discussing such topics as empathic distress, the top industry leaders that stood out from the pack this past year, a plausible link between white matter in the brain and Alzheimer's, and how a multi-use drug could benefit those combatting esophageal cancer.

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Ever felt like you were picking up someone's stress just from being around them? As if their experiences radiated and permeated your own mind? Well, studies being done at the Hotchkiss Brain Institute in the Cumming School of Medicine at the University of Calgary are studying precisely that.

Researchers have been told by healthcare workers that empathic nuances seem to transfer from soldiers' who suffer from PTSD to their partners or family members, despite never having served in the military. Jaideep Bains, PhD, and his team at the Hotchkiss Brain Institute (HBI) in the Cumming School of Medicine have discovered that stress transmitted from others can change the brain in the same way as real stress does.

The research team studied the effects of stress in pairs of male or female mice. They removed one mouse from each pair and exposed it to a mild stress before returning it to its partner. They then examined the responses of a specific population of brain cells in each mouse, which revealed that networks in the brains of both the stressed mouse and naïve partner were altered in the same way.

"There has been other literature that shows stress can be transferred — and our study is actually showing the brain is changed by that transferred stress," says Toni-Lee Sterley, a postdoctoral fellow in Bains's lab and the study's lead author. "The neurons that control the brain's response to stress showed changes in unstressed partners that were identical to those we measured in the stressed mice."

The researchers discovered that the activation of the neurons causes the release of a chemical signal that acts as an "alarm pheromone" from the mouse that alerts the partner. The partner who detects the signal can then in turn, alert additional members of the group.

Bains adds, "What we can begin to think about is whether other people's experiences or stresses may be changing us in a way that we don't fully understand. The study also demonstrates that traits we think of as uniquely human are evolutionary conserved biological traits."

The study demonstrates that the effects of stress on the brain are reversed only in female mice following a social interaction. The residual effects of stress on neurons in females were cut almost in half following time spent with unstressed partners. However, this did not apply or ring true for males.

If some of the effects of stress are erased through social interactions, but this benefit is limited to females, this may provide insights into how we design personalized approaches for the treatment of stress disorders in people.

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I would also like to acknowledge this year's Biotechnology Focus top life sciences CEO picks from across the country. They are industry leaders who have stood out from the pack, and whose tenacity is

extremely admirable. They have captured the attention of the Canadian biotech investment community and are the cream of the crop as Chief Executive Officers on the Canadian biotech scene. With the help of some leading Canadian biotech analysts and investors, we've put together a list of who we think the Top 5 CEOs who elevate their companies are.

The criteria for making the list: They are CEOs who have delivered in the past and are with companies where they have a chance of delivering in the future. They aren't necessarily leading the biggest companies, but rather, they qualify because they are the best leaders.

Dr. Clarissa Desjardins is a co-founder of Clementia Pharmaceuticals and has been the president since its inception in 2010 and chief executive officer since 2012. Her company is a clinical-stage biopharmaceutical company that develops disease-modifying treatments for patients suffering from debilitating bone and other diseases.

Cameron Piron is an industry-recognized leader and innovator in image-guided surgery. Although he is not a CEO, he has made a profound impact as a co-founder and president at Synaptive Medical – a company that is breaking ground with advanced medical devices, medical imaging and information science. Their BrightMatter technology combines surgical planning and navigation, robotic digital microscopy and informatics to create a family of devices to obtain patient data and retrieve it when needed the most.

Dr. Ali Tehrani is a co-founder, president and chief executive officer of Zymeworks Inc., and an obvious choice for this year's list. He has been an integral part of the success of Zymeworks, which continues to partner and flourish at a dizzying rate. The company's lead clinical candidate, ZW25, is a Azymetric bispecific antibody that targets two distinct domains of the HER2 receptor resulting in multiple differentiated mechanisms of action.

Carl Hansen started AbCellera working out of his laboratory at the University of British Columbia in 2012. He is the president and CEO of this privately held biotech company that provides enabling technologies for the discovery and development of monoclonal (mAb) therapies directly from natural immune cells. AbCellera's lead technology is a proprietary single cell antibody discovery platform that provides researchers the opportunity to rapidly identify mAb therapeutic candidates from the natural immune repertoires of any species.

Lloyd Segal, a veteran biotech executive, president and CEO of Repare Therapeutics was another indisputable choice for this list. Lloyd is an entrepreneur-in-residence at Versant Ventures, and from 2010-2016 was a managing partner at Persistence Capital Partners, a leading healthcare private equity investor. He held CEO roles at Caprion Pharmaceuticals, which he co-founded, Advanced Bioconcept and Thallion Pharmaceuticals, and has served as a director of several public and private corporations in the U.S. and Canada. Repare is developing new, precision oncology drugs for patients that target specific vulnerabilities of tumour cells. Its approach assimilates insights from several fields of cell biology including DNA repair and synthetic lethality.

There was no shortage of great candidates for this year's top biotech CEO picks. After so many outstanding nominations, it was hard to narrow it down to just five. Here are some of the Honourable mentions who just missed the cut:

Roberto Bellini – President and CEO of Bellus Health

Richard Glickman – Founder and CEO of Aurinia Pharmaceuticals

Arun Menawat – CEO of Profound Medical

Sammy Farah – President and CEO of Turnstone Biologics

Anthony Cheung – President and CEO of enGene Inc.

David Main – President and CEO of Aquinox Pharmaceuticals

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Scientists from Sunnybrook Hospital in Toronto have discovered that the white matter found in the brain chips away at memory by shrinking the brain and contributing more to dementia than previously thought.

White matter hyperintensities (WMH) are bright spots on MRI scans – tissue in the brain that is wearing away due to effects of aging and vascular risk factors on the brain's small vessels.

The research, published in the February 2018 issue of the journal Neurology, showed that individuals with extensive small vessel disease had profound shrinking of the temporal lobe, an important brain region that is instrumental to learning and memory function. The study included over 700 participants of the Sunnybrook Dementia Study led by Dr. Sandra E. Black. The researchers' analyses showed that shrinkage of the temporal lobe explained how WMH were associated with memory problems.

WMH is associated with poor verbal recall more so due to temporal lobe shrinkage and deficits in recognition memory – the most sensitive and specific cognitive sign of Alzheimer's disease – in people with Alzheimer's disease and across other late-life dementia syndromes including post-stroke dementia.

The researchers stress that small vessel disease is often a "silent" contributor to cognitive decline and dementia, as do large vessel strokes. Since small vessels are linked to brain shrinkage and memory problems it is important to recognize vascular brain disease as a potential "root cause" for dementia.

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Faculty of Medicine scientists at the University of British Columbia have discovered that a drug currently being tested for autoimmune disorders of the blood may also be a knight in shining armour for those with esophageal cancer.

Shane Duggan, a postdoctoral fellow in the division of gastroenterology, and Dermot Kelleher, dean of the faculty of medicine, found that fostamatinib reduced the growth rate of esophageal adenocarcinoma in mice by at least 70 per cent compared to the control growth.

Esophageal cancer has abysmal survival rates (only 14 per cent alive five years after diagnosis) and is a growing Canadian health concern.

The scientists published their discovery in Cellular and Molecular Gastroenterology and Hepatology explaining their search for possible treatment targets for esophageal cancer – the sixth-leading cause of cancer-related mortality and second-deadliest form of cancer.

Duggan and Kelleher conducted a screen of about 6,000 genes found in a cell that are known or emerging drug targets in a variety of diseases. They found about 300 druggable genes specific to esophageal cancer and using biopsies of esophageal cancer from Br

itish Columbia, the U.K., and Ireland, they narrowed that list to three primary candidates. It was then that they noticed something surprising – the genes were more associated with immune cells than with the epithelial cells of the esophagus.

Esophageal cancer is often preceded by a condition called Barrett's esophagus, which results from gastroesophagealreflux disease (GERD). The reflux causes the inflammation and induces the esophageal tissue to transform into intestinal-like tissue. The immune cells unleashed by GERD may never fully depart from the esophagus, causing low-level inflammation that continues undetected and without symptoms. The transformed esophageal epithelial cells, after prolonged exposure to inflammation, seem to produce and become driven by a protein called spleen tyrosine kinase (SYK).

Duggan and Kelleher then turned their attention to fostamatinib, an SYK inhibitor developed by San Francisco-based Rigel Pharmaceuticals Inc., which has shown promise in immune and lymphoproliferative disorders.

Proving them right, their study expressed that the drug was very effective at stopping the growth of esophageal cancer in vitro and in mice models that had been implanted with human esophageal cancer cells. While the tumours expanded rapidly in the mice in the control group, there was virtually no growth of the tumours in the mice given fostamatinib.

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Well that wraps up another episode! As always, if you have any questions or comments, I would love to hear from you, so feel free to email me at [email protected]. In the meantime, thanks for listening and hope you have a great week ahead! From my desk to yours – this is Michelle Currie.