Discovering biomarkers and new potential therapies | 091

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. This episode I will be discussing how new biomarkers found in maternal blood could prevent stillbirth, a new therapy for patients with partial spinal cord injuries, an investment from the Government of Canada, and Inversago closes their first series A financing round.   +++++  Researchers from the University of Alberta suggests new biomarkers found in maternal blood may help prevent stillbirth.  David Wishart, lead author and professor in the Department of Biological Sciences says, “When we started analyzing the blood of women who experienced stillbirth and compared them to healthy women, we noticed there’s a chemical difference. This suggested that we could predict and potentially prevent stillbirths.”  Using a mass spectrometer, Wishart and his colleagues identified four chemicals that showed up repetitively in mothers who experienced stillbirth. Combining this with demographic information about the mothers, the researchers discovered biomarkers for predicting signs of first-trimester stillbirth, including a fifth, previously unknown blood chemical called verruculotoxin.  Wishart explains that “Verruculotoxin is likely produced by microbes and fungi. This is intriguing because there’s anecdotal information about people living in certain areas, where there’s high mold, having a high incidence of stillbirth.”  Using this approach, scientists could develop tools and technology to screen for preventable illnesses that affect both women and children, explained Wishart.  Wishart says, “This research is the tip of a bigger iceberg. By looking at the chemicals in the mother’s blood, we can actually identify the risk for not just stillbirth, but a whole range of other conditions both for the mother and the fetus.”  Due to verruculotoxin being a newly discovered substance, further investigation and testing is required before a definite relation to stillbirth can be confirmed.  Previous research into predicting stillbirth has focused on genetics. Focusing on chemicals within the body gives scientists a clearer view of the potential causes and reasons. The technique also opens doors to other risk-related conditions that can happen during pregnancy.  Stillbirth is typically defined as fetal death at or after 20 to 28 weeks of pregnancy. It results in a baby born without signs of life. The term is in contrast to miscarriage which is an early pregnancy loss, and live birth where the baby is born alive, even if it dies shortly after.  +++++  New research from the University of Saskatchewan has scientists excited about the potential of a new therapy called acute intermittent hypoxia (AIH) for patients with partial spinal cord injuries.  AIH therapy involves repeated exposure to low oxygen (hypoxic) levels for brief periods. This action triggers a chain of events in the nerve cells or neurons as they react to the mild stress.  Valerie Verge, a professor of anatomy and cell biology in the College of Medicine says, “The acute intermittent hypoxia  AIH alerts the cells that they’re under stress. The cell adapts by turning on specific genes and creating specific proteins that help the cell to survive the stress. They induce a strengthening of the existing neuronal connections which is referred to as plasticity.”  As director of the Cameco MS Neuroscience Research Center, Verge has a keen interest in neurological research. She shares this passion with Dr. Gillian Muir, a professor at the Western College of Veterinary Medicine (WCVM) and the co-principal investigator in a recent study published in PLOS ONE.  While Verge’s focus is on the cellular level, Muir is an expert in behavioural recovery after injury. She has collaborated on studies with professor Gordon Mitchell, a noted neuroscientist at the University of Florida, and she has been involved in multiple studies monitoring the functional recovery that occurs when AIH acute intermittent hypoxia  therapy is combined with rehabilitative training in patients with spinal cord injuries.  Muir says, “The focus of this recent study was to look at what was changing in the cells of these animals in response to both the hypoxia exposure and the rehabilitative training. We looked for hypoxia-associated proteins, evidence that the cells were responding to the low oxygen, and we also looked for proteins associated with the plasticity—the proteins involved in strengthening connections between neurons.”  The study used two groups of rat models with partial spinal cord injuries that received seven days of rehabilitative motor therapy, with only one group reviving the AIH acute intermittent hypoxia  therapy along with the daily regime.  Each AIH treatment consisted of 10 five-minute cycles where the animals breathed hypoxic air (11 per cent oxygen) alternating with normal air (21 per cent oxygen). The research team compared the abilities of both groups each week as they performed specific motor tasks that had been mastered before the injury, and then they compared the cells in the spinal cords of both groups of animals. Results confirmed that AIH leads to increases in the amount of specific proteins within cells linked to hypoxia and plasticity. They also observed notable improvement in the functional abilities of the group that received both AIH and rehabilitative therapy.  Muir says, “We think that this combination of treatment is important because the AIH makes the cells more accessible to plasticity—that is, more amenable to making stronger connections with other neurons. The rehabilitation training activates the correct neural pathways and ensures that the appropriate neural circuitry becomes stronger.”  There have already been clinical and preclinical trials done in the States demonstrating that patients with spinal cord injuries who received AIH therapy could walk farther for longer and with improved ability.  A noteworthy finding of the current study was evidence that the proteins connected with plasticity were increased in areas of the spinal cord other than just the injury site—an indication that hypoxia triggers a reaction from neurons in other parts of the body, including the brain. Since AIH treatments expose the whole body to hypoxia, it’s possible that the nerve cells of the peripheral nervous system and the brain are also reacting to the low-level stress by creating the proteins associated with plasticity.  Verge and Muir are optimistic that AIH therapy will have a positive impact on a large spectrum of injuries and conditions that affect the nervous system; and although it is still too early to say, this study prompts further questions to the possibilities of AIH therapies and whether it can enhance the nervous system or even repair damaged cells.  +++++  There is a wide spectrum of health conditions from diabetes, mental health, and cancer that affect the Canadian population. These diseases pose a serious health risk to patients and the Canadian health system, and novel solutions are sorely needed. Promising advances may soon be close at hand thanks to an investment from the Government of Canada and several provincial and international partners and research institutions that will allow scientists to test-drive new ways to treat disease and improve patient care to see if they work in the real world.  Sonia Sidhu, Member of Parliament for Brampton South, on behalf of the Honourable Ginette Petitpas Taylor, Minister of Health, announced an investment from the Government of Canada, through the Canadian Institutes of Health Research, of $9.3 million while visiting St. Michael’s Hospital, where three of the research projects will be based.  The program, known as the Innovative Clinical Trials Initiative, will include additional funding of $13.3 million from partners, for a total investment of $22.6 million.  The investment will provide support over the next four years to seven research projects tackling a range of health issues that matter to Canadians:  -Reducing the incidence of diabetic foot ulcers – one of the most common and feared side-effects of diabetes, which, if left untreated, can lead to amputations;  -Reducing the number of unnecessary x-rays and pre-operative tests administered to patients;  -Supporting doctors to improve opioid- and antibiotic-prescribing practices;  -Reducing childhood obesity by re-examining the consumption of low-fat versus whole milk;  -Improving care and outcomes for patients admitted to intensive care units;  -Helping patients with multiple complex conditions navigate the health care system; and  -Improving care and recovery for young adults experiencing their first episodes of psychosis, such as schizophrenia.  The Honourable Ginette Petitpas Taylor, Minister of Health says, “Our Government proudly supports science because it has the power to change lives. The projects we are investing in today bring the promise of new treatments and improved quality of life for people with diabetes and mental illness, new insights into tackling childhood obesity, and new tools for health professionals to make the health care system more sustainable and work better for patients.”  Life sciences is an industry that is filled with innovation and offers much economic promise for governments who desire to grow a knowledge-based economy.  +++++  Inversago Pharma recently closed their first Series A financing round at $7 million. They join Accel-RX’s growing portfolio of promising next-gen Canadian start-ups, as well as co-investors Genesys Capital, AmorChem, Juvenile Diabetes Research Foundation T1D Fund, Anges Québec Capital as well as several angel investors.  Inversago is developing new generations of CB1 receptor inverse agonists. First generation CB1 blockers were previously in development for a range of metabolic conditions but were permeable to the blood-brain barrier and targeted brain CB1 receptors. This brain occupancy led to psychiatric adverse events which caused the termination of all CB1 inverse agonist programs.  The company’s technology, based on the work by CB1 world expert, George Kunos at the National Institutes of Health, has demonstrated that peripherally restricted CB1 blockade in preclinical models provides an equivalent therapeutic potential to treat conditions such as Obesity, NASH, type-1 and 2 Diabetes, Liver & Lung Fibrosis, without causing the CNS or behavioural effects associated with the earlier generations of CB1 blockers. The proceeds from this first round of financing will allow Inversago to focus on its first target indication, Prader-Willi Syndrome, an orphan disease that often leads to obesity and type-2 diabetes, as well as explore potential in type-1 diabetes.  Accel-Rx president and CEO, Natalie Dakers says, “Inversago’s technology could provide game-changing treatments for a number of metabolic diseases with few treatment options. Their novel approach to resolving prohibitive concerns involving the brain associated with this class of drug meshes with our investment philosophy of backing companies whose solutions are both innovative and designed for broad impact.”  This is Accel-Rx’s tenth investment in a portfolio that includes disruptive treatments and technologies to innovative approaches to neurodegenerative diseases, including Alzheimer’s and Lou Gehrig’s Disease.  Inversago founder and CEO, François Ravenelle says, “We are pleased to join the Accel-Rx portfolio of innovative companies and are grateful for their help in securing the two lead investors and spearheading the diligence efforts. Their involvement was instrumental in the success of this round and will enable the company to advance its program into clinical trials.”  Since 2014, Accel-Rx has screened over 200 early-stage companies from across Canada, selecting ten for investment and attracting an additional $44.6 million in co-investment thereby leveraging their initial capital outlay by more than 9X.  +++++   Well that wraps up another episode of Biotechnology Focus radio. Make sure to tune in next week to hear what is going in the life sciences sector from coast to coast. From my desk to yours – this is Michelle Currie.