Matters of the Mind

By Linda Quattrin

an overview of Ontario’s neuroscience excellence

If it were an infectious disease, the prevalence would qualify as a global epidemic. The constellation of neurological and psychiatric-related disorders – from Alzheimer’s to anxiety – touches fully one in three Canadian families, according to Neuroscience Canada. And the picture, as we know, is only getting greyer given the aging demographic in the developed world.

With the enormity of this challenge also comes tremendous opportunity: the opportunity to grow a signifi cant neurotechnology industry from Ontario’s already extensive track record in neuroscience research. At stake are huge economic rewards, long-lasting effects on employment, infrastructure development and regional competitiveness. Devices aside, the global neuromedicine market alone is valued at over USD$144 billion and has become larger than any other therapeutic market with projected market growth of 10 per cent per year, outpacing both cancer and cardiovascular markets.

So where do Ontario’s strengths lie?

In 2009, a group of distinguished international scientists took an in-depth look at the province’s research prowess. Led by eminent Canadians Dr. Joseph B. Martin, Dean Emeritus, Harvard Medical School, Joseph L. Rotman, businessman and philanthropist, Dr. Fergus Craik, Professor at the University of Toronto and Rotman Research Institute and Dr. Richard Murphy, President and CEO of Salk Institute for Biological Studies (retired), here’s a snapshot of what they found:

MOLeCuLar and CeLLuLar BiOLOgy

Ontario is rich in capable molecular neurobiologists working in cell biology, signal transduction, neural development, the regulation and plasticity of synaptic transmission, neurotransmitter receptor biology and RNA biology. A major focus of Ontario neurobiologists is in characterizing fundamental molecular mechanisms mediating neural transmission. Many Ontario researchers have made transformative discoveries on the fundamental principles of neurotransmitter release and uptake at nerve-cell-connecting synapses in the brain and spinal cord.

neurOdegenerative diseases

University of Toronto has an impressive array of affi liated research hospitals: Baycrest, Bloorview Kids Rehab, Centre for Addiction and Mental Health (CAMH), Hospital for Sick Children, Mount Sinai Hospital, St. Michael’s Hospital, Sunnybrook Health Sciences Centre, Toronto Rehab, University Health Network and Women’s College Hospital, many of which have long and storied traditions in outstanding neuroscience research. That strength extends outward in Ontario, with nodes of cross-disciplinary expertise in Alzheimer’s, multiple sclerosis, Parkinson’s and beyond.

genetiCs and genOMiCs

Ontario geneticists have made major contributions to understanding the genetic infl uences that contribute to neurodegenerative diseases and psychiatric diseases. Some highlights: • Researchers at Toronto’s Centre for Addiction and Mental

Health have been leaders in relating gene variants in the receptors for dopamine and serotonin to psychiatric disorders and to treatment response. • CAMH researchers have led important investigations into unstable DNA mutations in mental illness and are expanding that work to a range of disorders. • New lines of research include: combining genotyping and

MRI to explore genetic determinants of stroke recovery; and pharmacogenetic studies— discovering gene variants associated with good and bad responses to specifi c drugs— an area with great commercial potential. • The Centre for Applied Genomics at the Hospital for Sick

Children is a fast-growing centre producing excellent research on autistic spectrum disorders.

deep Brain stiMuLatiOn (dBs)

Toronto has one of the largest neurosurgery clinical and teaching groups in North America, and the Department of

Neurosurgery at Toronto Western Research Institute is cited by the US National Institutes of Health (NIH) as a world leader in DBS technology, which is being used to treat patients with treatment-resistant depression and Parkinson’s disease. This group published the first reports of using DBS for treatmentresistant depression.

Brain iMaging

Brain imaging (also called neuroimaging) is a major strength in Ontario, with a high concentration of research in MRI, PET, MEG, EEG and some optical techniques. Major centres include the Rotman Research Institute at Baycrest, Sunnybrook, Robarts Research Institute at London’s University of Western Ontario, CAMH, and, for complementary mouse imaging, a consortium of hospitals and their affiliated research institutes, including Mt. Sinai Hospital, the University Health Network and the Hospital for Sick Children.

COMputatiOnaL neurOsCienCe

This discipline is an Ontario strength as well as a clear need in contemporary neuroscience research. It is increasingly essential as a means to understand how both cells and brains compute and to model the interfaces between levels of function (e.g., between cells and circuits and between patterns of neural activity and cognitive performance). Institutional strengths are found in the psychology and computer science departments at the Universities of Ottawa, Toronto, Waterloo, and York. Scientists have developed computational models of neural network mechanisms responsible for high-level cognition, including analogy, concept application, theory evaluation, and emotional decision-making. Others have developed algorithms to simulate (and thus understand) learning processes in the visual system.

Learning and MeMOry

Cognitive neuroscience has been an internationally recognized strength of Ontario and of Canada generally for at least 50 years, with theoretical and experimental studies of human memory foremost in the cluster. Strengths include theoretical models, applications to neuropsychological cases, and the neural bases of memory via neuroimaging. A further focus has been the understanding of normal age-related declines in memory, with the group at the Rotman Research Institute Kdesignated as “best in the world” during a recent site visit. Brain pLastiCity C M Y Scientists around the province are working on plasticity, from genes to behaviour and rehabilitation. Efforts are also being made to link plasticity and neural regeneration to stem cell biology. Induced pluripotent stem cells (iPS cells) are being developed to create nerve cell diseases in a dish as well as patient-specific stem cells, with the goal of using such cells as substrates for drug toxicity experiments and therapeutics. In addition to making discoveries on molecular mechanisms regulating synaptic transmission, Ontario researchers have made major discoveries on mechanisms of learning and memory, and their dysfunction. Examples of key discoveries include neuronal competition in memory formation, the erasure of fear memories in the amygdala, and the role of the anterior cingulate cortex in fear learning.

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perCeptiOn and aCtiOn

Ontario has notable strength in studies of the relations between visual perception and motor action, and investigators have recently formed a consortium of 33 scientists (CAPnet) drawn largely from Toronto’s York University, Kingston’s Queen’s University, and the University of Western Ontario in London. CAPnet’s research goal is to understand how the brain uses sensory information to construct an internal perceptual representation of the world that guides purposeful movements, both in health and in sickness.

strOke

The province has established a strong network for the prevention, care, education and treatment of stroke patients.

Because vascular incidents have been associated with many forms of cognitive decline and dementia, the stroke network links stroke with neurodegenerative disease and cognitive and behavioural changes. Insights from work done by the

Centre for Stroke Recovery—involving scientists and clinicians from Ottawa and Toronto – have led to the important realization that there is time to interfere therapeutically to return blood flow to the affected region, which in turn led to the successful tissue plasminogen activator (tPA) therapy in acute stroke.

MediCaL deviCes

Ontario’s medical device community is extremely active, with critical mass and expertise. Strengths include: • Microfabrication, nanotechnology, EEG (64-channel recording), and microfluidics, which could lead to lab-on-a chip analysis and implantable devices. • Intelligent in-home technologies for supporting the daily

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“The most significant work coming out of Rotman has to do with the recognition that the aging brain is in fact…malleable,” said McIntosh. “The notion was for a number of years that once you’re past 20 to 25, the brain doesn’t change anymore - what we’ve shown is that the brain does change the way it does things pretty much across its lifespan. There is this idea of plasticity or adaptability that’s in brain function throughout life, and what that does is it actually provides the potential, i guess you could almost say hope that you can make use of that flexibility, then potentially remediate cognitive function.”

It truly is hope to the millions affected by these problems, a fact that certainly isn’t lost on McIntosh. The translation from research to reality can be long and arduous but these problems are fast becoming some of the most pressing concerns in life sciences.

“There’s been a difficulty I think with that translational aspect. Part of it is structural, in that a lot of research is done without a direct link into the clinical domain and part of it is sociological as well; once this stuff gets published it takes a while for it to filter down to be applied into things,” he said. “There are models developing. That’s one thing we’re trying to do at Rotman, it’s trying to make sure that the clinical research and the translational component is actually part of the way the institute is structured. So that when there is the potential for translating the basic findings into a clinical or applied domain, we can do that in-house and actually get the validation part of it done much more rapidly. That way you facilitate the translation so it is, in fact, implemented much more quickly.”

With baby boomers now reaching their ‘golden years’ there is an urgent need for new treatment options for the unprecedented large proportion of older Canadians. It makes the CNS field and particularly RRIs groundbreaking research very timely. In the past, McIntosh says that neuroscience has been about explaining things after it’s too far-gone. Now a shift is occurring where trying pick up the warning signs early is taking over as the dominant view point.

“As people age the number of these core morbidities are going to factor into quality of life and become more difficult to manage so the more we can get it early, the better off we are,” said Dr. McIntosh. “That’s why I think it’s important to not only understand the disease brain but what keeps the brian healthy for a longer period of time. And that’s why this research into the brain and aging is so important because we can understand not just the bad parts about aging and the brain but also the good parts and how to make the good parts more prevalent for the boomers.”

living of elderly people, such as monitoring home settings to detect falls, talking systems to prompt or instruct dementia patients through basic routines and eye-tracking technology as a diagnostic for stroke and Parkinson’s disease. • Virtual reality robotics, now in development for testing sensory, motor and cognitive function, as well as rehabilitation robotics.

Developing the ecosystem to effectively move these and other promising discoveries out of the lab and into the marketplace is at the heart of the mission of MaRS Discovery District. Located in Toronto and networked across Canada and internationally, MaRS is focused on building Ontario’s next generation of technology companies – in life sciences and health care, information and communications technology, cleantech and innovative social purpose enterprises.

Working with a range of public and private-sector partners – from an architecturally inspiring urban location where more than 2,000 people across the innovation spectrum come to work each day – MaRS provides entrepreneurs with business advice and mentorship, market intelligence, entrepreneurship education, seed capital and access to critical talent, customer and partner networks. And with more than 1,700 entrepreneur-clients served across the province since MaRS began offering advisory services in 2006, the critical mass in commercialization is clearly building in Ontario.

Linda Quattrin is Director, Communications at MaRS Discovery District. Her work involves engaging scientists, entrepreneurs, stakeholders and the media in building and promoting the next generation of global companies from Canadian science, technology and social innovation. To learn more about MaRS, visit www. marsdd.com; to learn more about Ontario’s strength in neurotechnology, download MaRS’ 2009 report here: http://www.marsdd.com/buzz/reports/neurotechnology