As the saying goes, a mind is a terrible thing to waste. The brain is the most significant contributor to making us what we are. Memories, personality traits, senses—you name it, it’s all stored or processed by the grey matter between your ears. Unfortunately, the fact that we as a people acknowledge this has little bearing on the battle that the global community is waging against brain disease, which includes Parkinson’s disease, Epilepsy, Huntington disease, Multiple Sclerosis, Cerebral Palsy and Alzheimer’s disease.
To determine the precise cost of these diseases to Canadians and our economy, the Public Health Agency of Canada announced a plan in 2009 to undertake a four-year study whereby gaps in our knowledge will be filled and a comprehensive report will help guide future expenditures.
Provincially, Ontario is firmly positioned on the front lines of this battle, which it estimates will cost $39 billion annually, with approximately $7.5 billion in direct costs to our health care system.
With internationally renowned scientists supported by worldclass technology and facilities, Ontario is poised to put all manner of brain disease on the run. Since 2003, the Ontario government has invested more than $99 million in 166 brain research projects across the province. There is incredible research happening quite literally across the province.
“Ontario is well-positioned with its concentration of worldclass research institutions and scientists to spin off companies that will develop innovative therapeutic treatments for neurological disorders,” says John Milloy, Minister of Research and Innovation.
At BIO 2010 in Chicago, Ontario’s Ministry of Research and Innovation (MRI) is focusing on Ontario’s strengths in neuroscience and fighting brain disease with a new Life Sciences Commercialization Strategy aimed at helping Ontario become known as “The Go-To Place” for innovative, multi-national pharmaceutical and advanced health technologies firms looking to source new technologies, and to test promising new therapies.
“Our strategy will fold existing MRI life sciences initiatives into a comprehensive new plan—allowing for better co-ordination, and to help position Ontario as one of the world’s best bio clusters,” says Milloy.
Take a look inside
Brain imaging is seen as the most important application for many modern imaging modalities. Magnetic Resonance Imaging (MRI), Computer Tomography (CT), Positron Emission Tomography (PET), Single Photon Emission Computer Tomography (SPECT) and combinations of these have contributed to enormous advances in the diagnosis of numerous neurological disorders. Advances in structural imaging using MRI and CT, and in functional imaging using fMRI and PET, are recognized as the most promising imaging technologies to aid in the detection of Alzheimer’s disease. Researchers believe that innovations in MR/PET will result in the development of new standards for assessing the pathologies and progression of neurological disorders, including Alzheimer’s disease, Parkinson’s disease, epilepsy, depression and schizophrenia.
The Robarts Research Institute at the University of Western Ontario, in London, is one of the household names in the global brain imaging community.
“If you attend the large imaging meetings, Robarts’ name is well recognized there,” says Dr. Robert Bartha, a scientist at Robarts and an associate professor in the department of medical biophysics at Western. “We’ve been lucky enough to attract some top people to our institute. We’re world-leading.”
According to the Alzheimer’s Society of Canada, in just five years, as many as 50 per cent more Canadians and their families than today could be facing Alzheimer’s disease or another form of dementia. Robarts operates with a broad focus on neurodegenerative disease, but with the rapidly aging population and growing incidences of Alzheimer’s disease, is it no wonder that a significant cross section of scientists at the institute are focusing on this particular disease.
“I look at the macroscopic, chemical or anatomical changes that happen in the brain as it progresses,” says Bartha. “There are also the people here who look at the cellular level, who try to understand the changes that occur and cause the disease to start in the first place.”
Alzheimer’s disease results in degeneration of tissue. Cells within the brain die, and using MRI technology, Bartha can essentially photograph this loss of brain mass over time. A normal brain will shrink naturally at a rate of about two per cent annually as a person ages. A patient with Alzheimer’s disease has a rate of two to three times that. In order to document this change, an MRI scanner, of which Robarts has four, is used because of the exquisite detail it can provide with soft tissue imaging.
MRI field strength is measured in Tesla units. Clinical MRI scanners, according to Bartha, operate at 1.5-tesla. In 1996, Robarts became the first and only facility in Canada (and one of very few in the world) to house a 4-tesla MRI scanner.
“A few years ago that unit was decommissioned,” says Bartha. To replace it, Robarts acquired one of the less than two-dozen 7-tesla MRI scanners in the world.
“We’re fortunate to have that here. It’s really a resource not just for our lab, but for all of southwestern Ontario. What’s funny right now is that the 7T unit doesn’t get a lot of use because it’s so new and some of the software and hardware is still being developed,” Bartha explains. “It’s not just cutting edge, it’s bleeding edge. We’ve had it for just over a year and we’re about 80 per cent of the way there to having it fully functioning.”
It is the hope of scientists at Robarts that this summer will see the beginning of regular, clinical work.
Culture of excellence
It isn’t luck that Robarts has taken a position as a world leader in the study of the brain. Indeed, Ontario has a culture of excellence in this area of study.
Baycrest’s Rotman Research Institute (RRI) was ranked among the world’s best in the field of aging-brain studies. According to the report, Neuroscience Industry Briefing: A review of Ontario’s R&D excellence with a focus on aging, after a five-year study, RRI was considered to be among such peers as the Massachusetts Institute of Technology (MIT) University College London (UCL), UC Berkley and the University of California, Los Angeles (UCLA). According to the review panel, “in the field of memory and aging, RRI scientists are probably the best in the world.”
One of the strengths of RRI is the scope of the goals its researchers seek. Dr. Randy McIntosh, Director of RRI, has spent the last four years, along with a consortium of about 14 other universities, working to develop what has come to be known as the virtual brain.
“We’re coming to an appreciation that the brain actually acts as a collaboration or a concert of networks that are interacting at different points of time to achieve a set of cognitive outputs,” says McIntosh. “One way we try to capture that is by analyzing the data from this whole brain perspective, much in the same way that you do geological mapping across the earth. What we use the virtual brain for is to pull together the wiring diagram showing the dynamics, in a sophisticated mathematical model, of the network interactions that take place when you’re doing anything from finger tapping to high cognitive functions. We’re constructing a brain here that really does everything our human brain does.”
This network of hardware and virtual components will eventually be able to mimic the way the brain adapts to disease and injury. It will be used to substantiate the relearning rules, to see how the brain attempts to adapt and recover from a lesion, or how the brain tries to stave off the effects of degeneration that you might see with Multiple Sclerosis or dementia.
“Unfortunately, there is a limitation in the process, in that we don’t know a whole lot about these diseases to begin with,” McIntosh says. However, benefit can still be gained from inputting our insufficient data into the virtual brain. “The system can help tell us what information we’re missing. It gives us a reality check in terms of what we don’t know and gives us direction as to what information we need in order to make the model more accurate.”
This is a rare and ambitious project. Similar systems do exist—one in Switzerland, another in Seattle—but nothing to this scale.
“This is rare because it’s a lot of work; nobody’s silly enough to start something like this,” says McIntosh.
As part of Ontario’s focus on neuroscience at BIO 2010, the province will host a Virtual Brain Symposium to support this world-leading research initiative.
Work at RRI is intertwined. Dr. Tomas Paus, for example, is beginning a transgenerational study on how genetics and environment can affect the brain. This includes, among other things, how brain disease is affected by these factors.
“I’m interested in collecting and analyzing extremely large datasets,” explains Paus. “Our data could feed very nicely into the virtual brain, because large datasets provide the basis of the whole virtual brain project, and we could learn much from it as well.”
There are many studies around the globe similar to that which Paus is undertaking. However, what’s unique about Paus’ work is that no previous study has attempted to go as deep. By exploring genetics and environment, Paus has the potential to unearth early warning signs of brain diseases that have until now gone unnoticed.
Early warning signs of Alzheimer’s disease, for example, are virtually unknown to the research community.
“Right now, we’re treating people at the end stage. That’s what Alzheimer’s is,” says Dr. Sandra Black, Neuroscience Program Research Director at Sunnybrook Research Institute, a worldleading brain research facility in its own right. “This disease is incubating in the brain for as long as 40 years, by the time people get to the point where they know they have the disease, it’s actually at the fourth stage of its development.
Additionally, the approach that Paus may use for his study is of an innovative and radical design.
“What we are thinking about, and this is still very preliminary, is to have phenotyping units out in the communities. We would have four different locations in Toronto- Scarborough, Mississauga, downtown and midtown and in some of those locations we would put MR scanners. We would have our staff there and all the other equipment. All the testing will be happening in those communities rather than at these hospitals. Of course you can imagine that it may not be only about acquiring data, but also that may be a unique opportunity for outreach. Selling science to youth, to the communities and having them participate in different ways,” says Paus.
This next step in his research builds on more than two decades of previous study and, he believes, will lead to much richer data than ever before.
Brain research artillery
Robarts and RRI are just two of many of Ontario’s institutions fighting to expose the workings of and cures to degenerative brain diseases.
Toronto’s Sunnybrook Research Institute is producing groundbreaking research in the areas of Alzheimer’s disease and stroke.
“We see that a lot of people who have died are not expressing a single disease. It’s actually a combination of Alzheimer’s and vascular disease,” explains Black. “The relationship of the two is starting to catch on, and we’re leading the way.”
As medical science becomes more successful in helping people survive cancer and heart disease, Black says, an unintended consequence is emerging, one which is called old age.
“This is going to be increasingly dominated by these disorders, which is why it’s so important to be doing everything we can to treat them.”
The University of Toronto’s Centre for Research in Neurodegenerative Diseases (CRND) is another resource for Ontario’s brain research community. Under the directorship of Peter St. George-Hyslop, CRND has been the site for a number of important discoveries.
In 2000, St. George-Hyslop identified the key protein involved in the degeneration of nerve cells in Alzheimer’s patients, creating international buzz and raising the status of Ontario’s position in the research community. Seven years later, a team led by St. George-Hyslop isolated a gene responsible for Alzheimer’s, solidifying CRND’s reputation.
In 2003, a team at Toronto Western Research Institute (TWRI) led by Dr. Andres Lozano inadvertently discovered a potential treatment for Alzheimer’s.
Lozano was attempting to treat an obese patient using deep brain stimulation to reduce appetite, when the patient began to experience vivid memories. It is surmised that such a technique can be used in Alzheimer’s patients to restore cognitive function.
Toronto’s Hospital for Sick Children, with a research budget of more than $140 million, is Canada’s most research-intensive hospital dedicated to children’s health and is a world-leader in neurology and neurosurgery, epilepsy, stroke, multiple sclerosis and brain tumours.
Finally, McMaster University in Hamilton is the home to state-of-the-art imaging technologies, such as MRIs, PET and EEG facilities, at the Brain-Body Institute.
With so much happening, Ontario is taking a broad approach, targeting the genetics, imaging and stem cell research that can help lead to treatment for brain diseases that can occur at every stage of life.
“With Ontario’s Innovation Agenda, we are focused on discovering new ways to treat disease,” says Milloy. “Ontario has the largest hub of biomedical activity in Canada and the fourth-largest biomedical research centre in North America with over 25 globally recognized health research institutes. By targeting investment toward areas where Ontario already is a global leader, and by building on our greatest strength—the talent and ingenuity of our people—Ontario is harnessing innovation to ensure our economy is one of the winning economies of the 21st century.”
