Discoveries: contending with the superbugs | 082

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!   +++++  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.  +++++  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.  +++++    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.  +++++  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.  +++++  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.