Dr. Lara Boyd, Canada Research Chair, Michael Smith Scholar, associate professor in the Department of Physical Therapy and director of the Brain Behaviour Laboratory at UBC, had no inclination to study the brain when she was first treating stroke patients.
She had completed her Masters in Physical Therapy and was working as a physical therapist with stroke patients when she started to question if what she was doing was truly helping them. It was a turning point in her life: “I quit my job. My parents were pretty concerned. But it felt like there was no evidence to support what we were doing.”
She set out to find the evidence. Boyd completed a degree in neuroscience followed by a post-doctoral fellowship in neurology and cognitive psychology. She pursued stroke research and was recruited to UBC in 2006 and now runs her own laboratory.
Boyd’s lab uses a number of techniques including motor and cognitive testing, pulsed and repetitive Transcranial Magnetic Stimulation (TMS) paired with the BrainSight co-registration system, Functional and Structural Magnetic Resonance Imaging (MRI), and Electroencephalography (EEG).
One study she is excited about is the lab’s semi-immersive virtual game where stroke participants come in and play a game where they ‘catch an asteroid’ (on the screen, their hand looks like a spaceship) and throw it into the sun where it explodes. If the ‘asteroid’ gets past their hand, the world explodes.
“So we are looking at this acquisition of skill as it relates to white matter plasticity,” Boyd explains.
“The game is targeted to specific areas of the brain and related directly to the amount of skills you develop. The better you are at the game, the more you increase your skill, the more myelin you develop.”
Myelin is the fatty insulation that sheaths nerve cells and Boyd suspects that the insulation may change in stroke patients. Boyd has collaborated with Alex Mackay, professor in the Department of Physics and Astronomy and head of the MRI Research Group at UBC, who developed a unique MRI scan that looks at the thickness of myelin. With this new information, Boyd is able to study how myelin might be improved through practice and training in stroke patients.
Boyd notes that stroke is the third leading cause of death in Canada and the primary cause of long-term disability in adults. Preventing brain loss can be mitigated to some extent by early detection: “If you do have a stroke, and can intervene very early — you have only four hours — you can save a lot of brain.”
However, most stroke sufferers lose brain cells that can result, says Boyd, in “severe functional limitations.” Her research is focused on taking “advantage of the remaining brain and stimulating plasticity in it that can then help to take over lost functions.”
While there are no interventions that can prevent stroke, Boyd is optimistic about what the new DMCBH might bring to her brain research:
Ask the Directors
You have hit your head and sustained a concussion. You are told it is not serious and to ‘take it easy for a few days’. Yet weeks later, you tire easily, you can’t concentrate and your thoughts are foggy. You just don’t feel like yourself.
What you’ve actually experienced is mild traumatic brain injury (mTBI) which, affirms Dr. Naznin Virji-Babul, Assistant Professor, Department of Physical Therapy at UBC, is a “major public health concern” and is presently “one of the least understood neurological conditions.”
Dr. Naznin Virji-Babul oversees the Perception-Action Laboratory in the Djavad Mowafaghian Centre for Brain Health (DMCBH). She cites Statistics Canada’s estimate that in Canada alone, some 98,440 people, 2.4 percent of those aged 12 and over, sustained a head injury in 2009-2010: “That’s nearly three hundred each day.”
With young brains especially, Virji-Babul says there’s an urgent need to understand the brain’s response to mTBI: “The risk of injury in pediatrics is a major concern because the brain is still developing and is known to be more susceptible to trauma.”
Virji-Babul has received funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) Engage program to develop sensors in ice-hockey helmets to wirelessly transmit information to a coach after a hit has occurred. Working with engineers at UBC and UCSD, she is also developing a headband for soccer players.
The other aspect of mTBI that Virji-Babul is researching is the recovery and treatment of concussion.
“The standard practice is that you should rest until you are asymptomatic and then you slowly start getting back into your regular routine.”
But that might not be good enough. The challenge, especially with teenagers who compete in sports, is they are returning to the game before they are ready. Not only are they more susceptible to another injury, the long-term effects of a second — or sometimes third — concussion can be quite serious and may not even be experienced until decades later.
Virji-Babul has found that the effects of mTBI are not transient; they’re cumulative.
Using functional magnetic resonance imaging (fMRI) to measure brain activity in adolescent brains in a resting state, Virji-Babul has discovered that teenagers who have experienced concussions have much more ‘active’ brains than their healthy counterparts which may explain the challenges with concentration and fatigue post-concussion. This discovery is a “powerful tool . . .to identify changes in brain function following brain injury and as a marker for tracking recovery of function.”
While there is no ‘cure’ for concussion, there are preventative measures to mitigate further risk of damage to young, still developing brains:
“If you suspect a concussion, get the child off the field,” advises Virji-Babul. “Better to be safe than sorry. Get the child evaluated by a physician. And don’t be in any hurry to get someone back into the game until you know they are better. We know now that concussion symptoms can last long after the injury occurs.”
Parkinson’s disease (PD) is due to the progressive degeneration and death of the central nervous system, specifically nerve cells in the mid-brain, leading to the loss of motor abilities, tremor, slowing gait, stiffness and ultimately, a wheelchair or worse. PD also eats into ‘non-motor’ functions that may include profound depression, problems with sleep, and cognitive decline.
Or as Matt Farrer, Canada Excellence Research Chair in Neurogenetics and Translational Neuroscience, starkly states: “It’s a dreadful disease.”
Common with the aging process, PD now affects one percent of the population at age 65 and up to four percent by 85. With no viable medications to halt PD, Farrer says “it’s progressive with huge costs to managing it and really, it’s just management.” Although certain medications can provide “some temporary relief . . . it’s palliative care; current medications do not stop the problem or slow it down.”
At the Djavad Mowafaghian Centre for Brain Health (DMCBH), Farrer and his colleagues are out to change this bleak prognosis.
Leveraging off of Farrer’s personal and professional connections to more than 20 major neurological centres worldwide, from Taiwan to Tunisia — “you name a country” — the effort is buttressed by DMBCH in-house expertise on all levels, fellow researchers not just involved in PD but ALS, MS, AD, epilepsy and other equally dreadful diseases.
A lot of it involves genetics, neuro-imaging and neuroscience and that requires public support and cooperation. It’s now paying off.
“With the help of patients and their families,” Farrer says the in last 15 years “remarkable insights” have been made in PD. Specifically, DMCBH investigators in genetics, “have directly implicated several mutant genes that predispose typical, late-onset PD.”
By fixing on “specific deficits in nerve-cell communications” involving these genes and the proteins they encode i.e. alpha-synuclein, leucine-rich repeat kinase 2, vacuolar protein sorting 35 and receptor-mediated endocytosis-8, Farrer is optimistic PD can be predicted and prevented.
Meanwhile, the DMCBH is working to head off the larger coming storm. By 2020, PD and similar brain-wasting diseases will overtake cancer and heart disease as the leading cause of death in Canada with one-in-two adults 85 years and older stricken with dementia. Farrer’s own father suffered from dementia at that age and died 10 years later. It was a long, difficult farewell and as populations age, one that will become increasingly more common.
Now that the DMCBH has opened, Farrer says optimal use of the facility means continued investment into operations and cutting-edge equipment needed by dedicated researchers to enable them to make discoveries to fast forward innovative new treatments.
While billions is spent on palliative care for neurodegenerative disorders, there is still relatively little investment to find out why some people are more susceptible, how their disease will progress or how it might be halted. Farrer hopes the new brain centre’s unique model will help bring profile and answers to these urgent questions.
Ask the Directors
To most people, an MRI (magnetic resonance imaging) scanner is the big, quietly humming machine into which you are slid and which uses magnetic energy to probe living human tissues on the cellular level. Your inner secrets — or rather ailments — are revealed, imaged on a screen. In 3D. It seems almost magical.
Physicist Dr. Alexander Rauscher, assistant professor and CIHR New Investigator at the UBC MRI Research Centre, sees it differently. Any MRI machine is basically like a huge, intricate smartphone that can’t do much without the ‘apps’ to fully explore the MRI technology’s exquisite, latent capabilities.
At the Djavad Mowafaghian Centre for Brain Health (DMCBH) at UBC, Rauscher and his colleagues are developing these vital MRI applications.
MRI science has been doing enormous good, notes Rauscher, giving the medical world ever-finer, ever faster, non-invasive, painless imaging. Rauscher adds that magnetic resonance has resulted in several Nobel prizes awarded to a total of eight Physicists and Chemists, spread out over six decades.
MRI machines are rated by achievable field strength or Telsas: the stronger the field, the finer, more sensitive and faster the imaging. For those dependent on the results, greater intensity means better diagnostics and improved prediction of outcomes.
The UBC MRI Research Centre makes state-of-the-art in vivo imaging and spectroscopy available to several Vancouver teaching hospitals and the broader research community. However, it all comes down to teasing out the information concealed in the MRI signals.
In what Rauscher calls “a famous example” of UBC expertise, Professor Alex MacKay and his team were the first to develop an MRI method to scan and measure myelin, the essential insulator surrounding nerve fibres. Recently, Rauscher and MacKay taught the MRI to run the myelin scan much faster, opening new avenues in brain research.
“The MRI scientists at the DMCBH continue to develop new methods for investigating the human brain,” says Rauscher. “They work on techniques that are extremely sensitive to injury in brain tissue, such as Multiple Sclerosis (MS), stroke, or traumatic brain injury. They have also developed techniques that are sensitive to tiny bleeds in the brains of people with Alzheimer’s disease, that can’t be seen with conventional MRI.”
At the DMCBH, researchers all benefit from the latest technology to speed up discovery and Rauscher is no exception: He hopes to have a ‘cutting edge’ 7 Tesla MRI (at a cost of $12 million dollars) which, used in tandem with a new 3 Tesla machine, would literally power up more and ever better MRI diagnosis and medical discoveries.
Not all ambitions for ‘bigger and better’ result in saving lives, but in this case they very well could.
As a UBC associate professor, medical physician, supervisor for a 20-strong clinical-trial team, and now a director of the Multiple Sclerosis and Neuromyelitis Optica clinics at the Djavad Mowafaghian Centre for Brain Health (DMCBH), Tony Traboulsee gives a quiet laugh, explaining: “It’s hard trying to figure out which hat you’re wearing at each hour of the day.”
While at the DMCBH, his ‘top of mind’ focus is ‘translational medicine’, taking new medical research from the ‘lab bench to the hospital bed’ in what is a gestalt of collaborative innovation.
“These new facilities bring researchers, patients and clinicians closer together,” explains Traboulsee. “This will improve the efficiency of projects, allow collaborations across disciplines and fast-track new discoveries that can impact on patient care.”
Traboulsee’s own specialty is multiple sclerosis (MS). Although the causes “remains a mystery,” he believes that, thanks to Canadian research, “especially research led by faculty at UBC over the past three decades,” MS researchers are zeroing in “on important environmental and genetic clues that will lead to better treatment and a cure.”
In brain-health treatment in general and MS specifically, Traboulsee points to the recent advancements and therapeutics to slow down or even stop disease progression.
“The time to diagnosing has sped up quite a bit and so that’s a good thing but it’s a good thing only if you can do something about it. In the past few years, the treatments for MS are just so dramatically different than what was available ten years ago. It’s really, really exciting to see the new treatments.”
Equally exciting is being so close to the action.
Specific to MS, Traboulsee says that in the last five to 10 years, he’s seen “some failures, some underwhelming drugs” but recently, “some amazing treatments” have appeared. For example, one MS-specific medication can “reset your immune system; it’s phenomenal. Half the people actually improve.”
Twenty years in development, it’s just coming to market in Canada and “because of the research we do here [at UBC],” BC has had early access through clinical trials and the highest North American usage with 60 people treated so far and with good results. “One guy is running for council of a big city. It’s had that profound an impact.”
It’s these victories that fuel Traboulsee’s optimism. With the DMCBH now open, he believes more good news will follow.
“MS research and treatments have had the greatest advances in any field of medicine over the past decade. At this rate of progress, and with UBC continuing in a global leadership role, we should see an exponential growth in success over the next 10 years.”
Mental Health and Addiction
It is a fact that people are more likely to talk about their physical ailments and pursue treatment for them than they are for mental illness. According to the Mental Health Commission of Canada, about 20 percent of the population is living with mental illnesses, many of which go untreated because of the barrier of stigma. Bell’s ‘Let’s Talk’ campaign, featuring Olympic athlete Clara Hughes as a vocal ambassador, has raised awareness (and $67 million) for mental health but there’s much more work to be done in finding better treatments and interventions for these often devastating illnesses.
At UBC, a variety of centres including the UBC Department of Psychiatry, the UBC Mood Disorders Centre, the UBC Institute of Mental Health and now the Djavad Mowafaghian Centre for Brain Health (DMCBH) are working in collaboration to address the disabling nature of many of these mental health disorders.
Dr. Raymond Lam is the medical director of the Mood Disorders Centre, which consists of an inpatient unit (1E) in the Detwiller Pavillion at UBCH and an outpatient clinic in DMCBH with both units funded by Vancouver Coastal Health. Mental health challenges affect one in five Canadians, says Lam and while common can be “disabling” for those affected.
Not surprisingly, the economic effect of mental illness is enormous. Lam cites a study done in Ontario that looked at health disability (a combination of years of life lost because of early mortality and years of life lost because of inability to function) and staggeringly “the burden of depression alone was greater than the combined burden of breast, lung, colorectal and prostate cancer.”
Lam’s research at DMCBH is looking at new treatments for mood disorders, including new medications, new psychotherapies such as cognitive remediation, and transcranial magnetic stimulation.
He is hopeful about the potential for collaboration at the new brain health centre because, he explains, “you are with other groups who all have the same mission.”
He urges people to help reduce stigma about depression and mental illness by learning about them and if they are struggling with depression, seek help from family and friends and/or a health professional because there is help available.
Similarly, Dr. Catharine Winstanley would like to eliminate the stigma around mental illness and hopes for the day when it can be proven unequivocally that it is a biological issue of neurons behaving in a particular way versus it being someone’s ‘fault’.
“Just as most of the illnesses we are familiar with, such as diabetes or hypertension, have a biological cause, the same is true for mental illnesses,” says Winstanley and suggests that we should “not be afraid to seek help when we feel our brains are not working right.”
As principal investigator at the Molecular and Behavioural Neuroscience laboratory, Winstanley is conducting a number of studies on impulse control and addictions, one of which has taken a one-of-a-kind approach to gambling addiction.
One of the lab’s innovative studies, lead by PhD student Paul Cocker, created a “casino-like” slot machine, using flashing lights and sugar pellet rewards, to study behaviour in rats.
Her team discovered that a type of drug called D4 antagonists, which work by blocking a specific type of dopamine receptor in the brain, help animals recognize a ‘win’ versus a ‘loss’ on the rat slot machine. In other words, says Winstanley, “it makes them less vulnerable to what is called the ‘near miss effect’ — that feeling of being closer to a win when two out of three symbols match- which we know motivates continual engagement with the game.”
While still in a preliminary stage, the hope is that dopamine D4 antagonists will be a treatment avenue for treating gambling addictions in humans.
Winstanley is encouraged by the potential of the new brain health centre to increase research innovation and thinks that by “bringing clinicians and neuroscientists who work on different disorders together under one roof, there are now fantastic synergies between research groups that really advance discovery in novel directions.”
Ask the Directors
ALS (Amyotrophic lateral sclerosis)
When Dr. Neil Cashman was a resident neurologist back in the mid 1980s, he served in the ALS (amyotrophic lateral sclerosis) clinic at the University of Chicago. It changed his career path.
“I had one year where I had three patients under my care, three teenage women, who died of ALS — and that just drove me up a wall. After that, I wanted more than anything, to do something that could help people with ALS.”
Today, there is still no effective treatment for what Cashman calls “the dreadful disease” which now afflicts approximately 3,000 Canadians and is invariably fatal.
However, as UBC Canada Research Chair in Neurodegeneration and Protein Misfolding, Cashman and his colleagues at the Djavad Mowafaghian Centre for Brain Health (DMCBH) are closing in on an immunotherapy and a possible cure. As Cashman quietly understates: “It would be huge.”
It’s now understood that amyotrophic lateral sclerosis (ALS) is transmitted through the nervous system by misfolded SOD1 (superoxide dismutase 1) protein molecules, which don’t ‘fold up’ in their normal 3-D shape. Instead, they basically turn inside out to display their ‘sticky’ innards, creating what Cashman calls “chaos” within the nerve cell. This chaos is also propagated to adjacent healthy cells in a stealthy cascade of neuron degeneration and death.
Misfolded or distorted proteins or ‘prions’ are also the principal factors in Creutzfeldt-Jakob disease (CJD), Alzheimer’s and Parkinson’s disease and other major human and animal brain and nerve-wasting killers.
In SOD1 deformation, Cashman wondered if a specific drifting fragment of exposed amino acids could be targeted in ALS propagation. He zeroed in on regions that are exposed in misfolded SOD1, and buried in the normally folded form.
The next step was to develop an antibody to specifically chase down and neutralize the SOD1 “bad guys” while ignoring the healthy form, effectively jam up the sticky, exposed innards of the malformed SOD1 protein and thus block ALS propagation at its molecular source.
Cashman and his colleagues have now developed such an antibody. The antibody has been tested in mouse models of ALS, and it works. Cashman says this research has applications for similar brain and nerve diseases. “It’s the same thing for Alzheimer’s, and a preventative vaccine for prion diseases.”
More than two decades on, Cashman can’t forget the awful year at the Chicago ALS clinic that still serves him as a compelling reason to find a cure. Today, at the DMCBH, he’s helping forge possible new futures for those suffering from brain diseases of all types.
According to the Alzheimer’s Society of Canada (ASC), the global prevalence of dementia stands to double every 20 years, to 65.7 million cases in 2030, and 115.4 million in 2050. In Canada and if no cure is found, 1.4 million people will suffer from the disease by 2031. Furthermore, the economic impact (direct and indirect) of the disease in Canada, notes the ASC, is $33 billion annually.
It is, by any definition, a health care crisis.
Dr. Haakon Nygaard is keenly aware of the urgency surrounding the need to understand and treat Alzheimer’s disease (AD). When you spend any amount of time with him, you can sense his deep commitment to the people who suffer from the debilitating disease and the families affected by their loved ones loss of ‘self’.
Nygaard, a recent recruit from the Faculty of Medicine at Yale, holds the Fipke Professorship in Alzheimer’s Research (Charles Fipke donated $3 million to endow a professorship) and now works out of the Djavad Mowafaghian Centre for Brain Health (DMCBH) at UBC.
Why his focus on Alzheimer’s?
“I connect with older people and enjoy working with them, so for me it was a natural population to work with. It gives me a sense of purpose to try to make a difference in these people’s lives.”
Nygaard warns that worldwide, AD is increasing with “roughly 40 percent of all persons above age 80, and their families, suffering from the disease.”
In his mission to find a cure, Nygaard is currently doing pre-clinical research to figure out why AD-afflicted neurons die. He believes that “if we can identify on the molecular level what pathways and what molecules are involved in causing the disease, then we can design a drug to stop this particular process. That’s the idea.”
Nygaard posits that by using a drug already been developed for another illness, you can “shave off many years of development and tens of millions of dollars.” Hence his current clinical trial to slow the progression of AD via the drug Saracatinib, initially developed to treat cancer patients.
His hope is that the new Djavad Mowafaghian Centre for Brain Health (DMCBH) will speed up the translation of “new findings borne out of basic research” to the patient.
As to what the average person can do to prevent AD, Nygaard suggest that basic good health — regular exercise, diet, and sleep — potentially offer a window to escape the disease: “If you can delay the onset of Alzheimer’s by only five years, you cut the prevalence of Alzheimer’s in half.”
Nygaard is vocal about the need for a collective effort in ending the devastating effects of the disease and suggests that we can all do something about it:
“My message would be to let your voice be heard. Get involved in raising money for AD research, and become part of the solution. Only together will we succeed in bringing an end to this terrible disease.”
Ask the Directors
Ask the Directors
Dr. Brian MacVicar, a Professor in the Department of Psychiatry, is one of the world’s pioneers in describing the activity of brain cells — not just neurons, but glial cells, thus contributing to a new appreciation for their essential roles in brain maintenance, protection and repair. Dr. MacVicar is the Canada Research Chair in Neuroscience, a Fellow of the Canadian Academy of Health Science and a Fellow of the Royal Society of Canada. He is also the Head of Basic Neuroscience in the Department of Psychiatry.
Dr. Jon Stoessl, a Professor and Head of the Division of Neurology and Director of the Pacific Parkinson’s Research Centre, is an internationally recognized Parkinson’s researcher and clinician. He uses positron emission tomography to study Parkinson’s disease and related disorders, the basis for complications arising from Parkinson’s treatment, and the mechanisms of the placebo effect. Dr. Stoessl is the Canada Research Chair in Parkinson’s disease and a Fellow of the Canadian Academy of Health Science.
People are living longer in developed and developing countries and it is predicted there will be a corresponding increase in neurological disorders around the globe.
If one feels helpless, it isn’t without good reason. There simply are few interventions that will cure, prevent or slow the progression of brain disease.
Dr. Teresa Liu-Ambrose, associate professor in the Department of Physical Therapy and director of the Aging, Mobility, and Cognitive Neuroscience Laboratory at UBC, says lifestyle changes can make a significant difference. “There is a growing recognition, at an international level, that there is a huge connection between how your brain is functioning and how you’re functioning physically.”
With advanced neuroimaging, exercise is shown to affect brain functions and brain structure. “We actually see increases in brain volume in very specific areas such as the hippocampus which is a primary brain region responsible for memory,” explains Liu-Ambrose.
In her Vitality: Promoting Cognitive Function in Older Adults With Chronic Stroke study, Liu-Ambrose examines the effects of exercise on stroke patients. One of her biggest fans of the program is Marco Chorbajian. Marco is a firm believer in the power of exercise and has regained an outstanding amount of mobility and increased his cognitive health as well.
It may seem obvious, but Liu-Ambrose says a healthy, balanced diet can improve your brain health too.
“Your brain is a metabolic organ that needs a lot of good nutrients in and out — good stuff in, bad stuff out. It is situated in this fluid that bathes it in nourishment. If that environment is altered, it compromises the organ as a whole.”
Like the many researchers now working in the clinics and labs at the new brain centre, Liu-Ambrose has found being under the same roof an advantage in her research. “At DMCBH, I work with a lot of neurologists, our research converges together and while we have different points of view they really are just different pieces of the same puzzle.
The synapses of discovery may have mysterious origins, but it is certain that the researchers (over 200) associated with the DMCBH are poised for innovations that will change the world.