Science
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! +++++ 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. +++++ 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. +++++ 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. +++++ 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. +++++ 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 press@promotivemedia.ca. Tune in next week! From my desk to yours – this is Michelle Currie.