Western neuroscientists and neurologists are combining efforts to develop more efficient ways to test the effectiveness of medication for neurodegenerative diseases – the leading cause of disability in Canada.
There are no successful drug therapies for brain conditions – like Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis, or ALS – and current clinical trials for neurodegenerative disorders fail 92 per cent of the time, with each misfire costing as much as $1 billion.
An interdisciplinary team of internationally renowned researchers are using innovative technology and advanced neuroscience techniques to bridge the gap between cutting-edge basic science and game-changing clinical discoveries. And this all happens with support from BrainsCAN, a neuroscience research initiative at Western supported by the Canada First Research Excellence Fund (CFREF).
Models and modern tech
Marco Prado, Canada Research Chair in Neurochemistry of Dementia, and Vania Prado, Schulich School of Medicine & Dentistry professor, start by developing animal models at the molecular and cellular level that better reflect human neurodegenerative conditions. This modelling allows the scientists to isolate disruptions in the brain, which cause the diseases, expediting discovery for new therapeutic targets.
Once successful, Lisa Saksida, Canada Research Chair in Translational Cognitive Neuroscience, and Tim Bussey, Western Research Chair in Cognitive Neuroscience, take over and run these animal models through their world-first touchscreen systems, allowing an unrivalled cognitive comparison for future human patients.
(Top, L-R) Penny MacDonald, movement disorders neurologist; Ali Khan, professor in medical biophysics and medical imaging; (middle, L-R) Lisa Saksida, Canada Research Chair in Translational Cognitive Neuroscience; Marco Prado, professor in physiology and pharmacology, anatomy and cell biology; Ravi Menon, director for the Centre for Functional and Metabolic Mapping; (bottom, L-R) Elizabeth Finger, neurologist; Adrian Owen, Koerner Fellow and co-director, CIFAR Program in Brain, Mind & Consciousness; Tim Bussey, Research Chair in Cognitive Neuroscience; and Vania Prado, professor in physiology and pharmacology, anatomy and cell biology
“To understand what goes on in the brain on a cellular and molecular level during drug testing, we need to do very precise and standardized tests for learning, memory and attention,” said Saksida, BrainsCAN scientific co-director.
Saksida and Bussey have developed a touchscreen system that allows researchers to study mice – using a computer game on a touchscreen tablet – in the same ways humans are examined. The mice interact with images on a screen by pressing them with their nose, and they get strawberry milkshake when they get the answer correct. Incredibly, memory, learning, and behaviour deficiencies seen in mice mirror issues detected in humans with brain diseases, making them a superior model for understanding brain disease.
Testing through imaging
Touchscreen testing, now considered a best practice among the international research community, creates the roadmap for accelerated drug therapies but a critical next step is recreating the findings in Canada’s only collection of high and ultra-high field magnetic resonance imaging (MRI) systems located at Western’s Centre for Functional and Metabolic Mapping (CFMM).
Researchers led by Ravi Menon, Fellow of the Royal Society of Canada, can peer inside both the mouse and the human brain to examine brain structure and activity, and more importantly, get detailed insight into whether drug treatments are positively impacting targeted areas of the brain.
“If you identify molecules or therapies that are going to work, you want to make sure they’re working on the right circuits or the right places in the brain. Imaging makes this happen,” said Menon, BrainsCAN scientific co-director.
Ali Khan, Canada Research Chair in Computational Neuroimaging, next analyzes the resulting MRI data to understand the disease-based disruptions in the brain at a level of detail not previously possible. This level of detail allows researchers to pinpoint exactly where in the brain clinicians should target with therapeutics. This information allows clinicians to make better decisions on how to treat patients.
The next step is moving this information from the lab to the clinic.
Patient testing
To ensure findings from animal studies are connected to human studies outside of the lab, Dr. Adrian Owen, renowned neuroscientist and Schulich School of Medicine & Dentistry professor, has taken these computer-based tasks used by Saksida and Bussey and created similar web-based tests for human participants. Using the online cognitive assessment platform, Cambridge Brain Sciences (CBS), participants complete memory, reasoning and concentration tests from their computer screens, providing researchers with baseline data for healthy participants. This allows health-care practitioners to compare CBS data with their patients’ cognitive performance – giving health-care providers a better understanding of a patient’s overall brain health.
Taking this one step further, neurologists at Western have integrated computerized testing into the clinic. Dr. Penny MacDonald, Canada Research Chair in Cognitive Neuroscience and Neuroimaging, and Dr. Elizabeth Finger, a professor in the department of clinical neurological sciences, are examining Alzheimer’s and Parkinson’s patients using the same computer-based testing used in mice. This integrated approach allows researchers to discover if positive outcomes in animal models can be converted to human patients.
With collaborative research efforts, innovative technology, and support from CFREF, Western is developing ground-breaking drug assessment techniques for brain diseases and disorders – moving ever closer to helping the nearly 3.6 million Canadians affected by a brain condition.
“We may not speak each other’s languages, but by putting researchers and clinicians together and coming up with a base understanding, it becomes a lot more productive in terms of using all of these sophisticated tools to determine whether a drug will work,” said Menon.
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