News Updates
Dr. Neil Cashman wins Genome BC Award for Scientific Excellence
The Brain Research Centre is pleased to announce that Dr. Neil Cashman has been awarded the Genome BC Award for Scientific Excellence. This award is presented annually by Life Sciences British Columbia to honor individuals who have received significant international recognition in the fields of genomics, proteomics, bioinformatics or systems biology.
Dr. Cashman, a Senior Investigator at the Brain Research Centre and Scientific Director of PrioNet Canada, was recognized for his instrumental role in translating research discoveries into therapeutics and diagnostics for neurodegenerative disorders, such as Alzheimer’s and amyotrophic lateral sclerosis (Lou Gehrig’s disease), and the discovery of protective vaccines for infectious prion diseases, including bovine spongiform encephalopathy (mad cow disease). Throughout the course of his career, Dr. Cashman has authored over 300 scientific publications, filed 30 patents, and has received numerous accolades for his ground-breaking discoveries and globally collaborative research efforts.
In an effort to bridge the gap between research findings and patient care, Dr. Cashman is a practicing neurologist with Vancouver Coastal Health and the academic director of the VCH ALS Centre. He has also founded two biotech companies, Caprion Pharmaceuticals and Amorfix Life Sciences, Ltd. and co-founded the Canadian Creutzfeldt-Jakob Disease (CJD, a human prion disease) Surveillance System, a network that monitors and tracks the diagnoses of CJD across Canada. In addition, to further Canadian prion research after the outbreak of mad cow disease in 2003, Dr. Cashman organized a Network of Centres of Excellence called PrioNet Canada, which brings together a network of multidisciplinary researchers nationally and internationally to investigate the causes and prevention of prion diseases. PrioNet Canada is hosted by UBC Faculty of Medicine and VCH Research Institute
Dr. Cashman also holds the Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases, is a Professor of Neurology at UBC and serves as an expert consultant for the Canadian government and international industry.
New drugs show promise for preventing “absence seizures” in children: UBC research
A team led by Brain Research Member Dr. Terry Snutch has developed a new class of drugs that completely suppress absence seizures – a brief, sudden loss of consciousness – in rats, and which are now being tested in humans.
Absence seizures, also known as “petit mal seizures,” are a symptom of epilepsy, most commonly experienced by children. During such episodes, the person looks awake but dazed. The seizures, arising from a flurry of high-frequency signals put out by the neurons of the thalamus, can be dangerous if they occur while a person is swimming or driving, and can also interrupt learning.
Available medications don’t completely control such seizures in many patients. They also cause severe side effects, including sleepiness, blurred vision and diminished motor control.
A Canadian-Australian team, led by neuroscientist Terrance P. Snutch, a Canada Research Chair in the Michael Smith Laboratories at UBC, developed new drugs with a different target – the flow of calcium into brain cells. Their findings were published today in Science Translational Medicine. [Read more]
Brain Research Centre researcher wins Innovation Award at Stroke Congress
Thomas Harrison, a member of Dr. Tim Murphy’s lab, earned top honors at the 2011 Stroke Congress for his research regarding the spontaneous reorganization of neural circuitry after stroke. Mr. Harrison’s research, which uses laser light to map the brains of mice after stroke and to track recovery, won the Innovation Award – a distinction that "highlights a study that brings a completely new approach to an important research problem with the potential for addressing questions that previously could not be investigated."
Mr. Harrison’s research looks into the plasticity of the brain and serves to dispel the popular belief that the brain is hardwired in adulthood. After suffering a stroke, the physical damage is irreversible but the brain is capable of spontaneous functional recovery, meaning the surviving brain cells will assume roles previously performed by stroke-affected cells. Although surviving brain regions are forced to compensate for a loss of neural circuitry, the process is necessary for recovery of function following severe injuries. [Read more]
Dr. Michael Krausz to lead million-dollar Bell Youth Mental Health IMPACT Project
(Dec. 9, 2011) On November 16, 2011, UBC and Bell announced a $1M gift to establish the Bell Youth Mental Health IMPACT project, which will be led by Dr. Michael Krausz, a Brain Research Centre member and UBC-Providence Leading Edge Endowment Fund (LEEF) Chair in Addiction Research at the Institute of Mental Health.
The Bell Youth Mental Health IMPACT Project will enable researchers from the University of British Columbia to conduct mental health outreach to youth in need. As part of the project, researchers will develop a mental health web portal that provides educational and self-assessment tools, automated feedback, a list of treatment options, advice on obtaining services, and coping techniques. Additional features, such as online consultations through e-mail, chat rooms, video-conferencing, instant messaging and social media tools, will be added in the future based on research into the effectiveness of this outreach model.[Read more]
Dr. Jack Taunton named 2011 BC Athletics Hall of Fame inductee
UBC Prof. Dr. Jack Taunton has been named the 2011 BC Athletics Hall of Fame inductee for his outstanding contributions as an athlete, community builder and sports medicine physician. BC Athletics presented Dr. Taunton, co-founder of the Allan McGavin Sports Medicine Centre, with the distinction on Sunday, December 3 during an award ceremony in Richmond, B.C.
“This award is a tremendous honour,” says Dr. Taunton, who served as Chief Medical Officer (CMO) at Vancouver’s 2010 Winter Games and was responsible for basic and emergency health care and doping control.
“It’s truly a case of a hobby going wild with an initial running career that led to starting up a sports medicine clinic with my partner Dr. Doug Clement and then my endeavours at UBC. It has been a great run.” [Read more]
Researchers' discovery may revolutionize treatment of ALS
A team of researchers from the University of British Columbia and the Vancouver Coastal Health Research Institute have found a key link between prions and the neurodegenerative disease ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig’s disease. The discovery is significant as it opens the door to novel approaches to the treatment of ALS.
A pivotal paper published by the team this week in the Proceedings of the National Academy of Sciences (PNAS), demonstrates that the SOD1 protein (superoxide dismutase 1), which has been shown to be implicated in the ALS disease process, exhibits prion-like properties. The researchers found that SOD1 participates in a process called template-directed misfolding. This term refers to the coercion of one protein by another protein to change shape and accumulate in large complexes in a fashion similar to the process underlying prion diseases. [Read more]
Vancouver research team plays key role in discovering the most common cause of ALS and Frontotemporal Dementia
Dr. Ian Mackenzie, neuropathologist at Vancouver General Hospital and professor in the Department of Pathology and Laboratory Medicine at UBC is part of a North American team of researchers who found a genetic abnormality they believe to be the cause of two major neurodegenerative diseases: FTD (frontotemporal dementia) and ALS (amyotrophic lateral sclerosis).
Led by neurogeneticist Rosa Rademakers at the Mayo Clinic in Florida the researchers found a short DNA sequence repeated hundreds to thousands of times in almost 12 percent of familial FTD and more than 22 percent of familial ALS of samples studied. [Read more]
The Brain Research Centre and the Centre for Drug Research and Development Collaborate to Bring New Therapies to Those Suffering from Neurological Disorders
The BRC and the Centre for Drug Research and Development (CDRD) have entered into a Preferred Collaboration Agreement. The two organizations will work together, sharing their resources and expertise to facilitate joint drug development research projects -- focusing on the acceleration of discovery, development and commercialization of technologies for the diagnosis and treatment of neurological and psychiatric disorders.
“Canada is well-recognized worldwide for our neuroscience excellence and our leading research nodes such as the Brain Research Centre,” said Karimah Es Sabar, CDRD Senior Vice President, Business and Strategic Affairs. “We are extremely pleased to be working with their team of top researchers to advance the development of their most therapeutically promising discoveries, while further achieving CDRD’s mission of translating promising research into viable commercial opportunities for the private sector.”
“The diseases that affect the brain represent the largest health challenge in Canada today. By bringing together the Brain Research Centre’s talented investigators who are discovering the mechanisms that underlie brain diseases and identifying therapeutic targets, with the drug development capabilities of CDRD, we create tremendous synergies, and facilitate the process by which new therapeutics are brought to the patient,” said Max Cynader, Director of the Brain Research Centre.
CDRD and the Brain Research Centre are now working together on a number of research projects. These include a collaboration with Dr. Cheryl Wellington, Associate Professor in the Department of Pathology and Laboratory Medicine at the University of British Columbia to screen for novel compounds which increase Apolipoprotein E lipidation in the brain as a therapeutic approach to Alzheimer’s disease. A second project is based on the research of Dr. Yu Tian Wang, Professor in the Faculty of Medicine at UBC, who has identified a novel peptide that slows down memory loss and may have therapeutic potential in mild cognitive impairment and early onset Alzheimer’s disease.
To these and other projects ongoing in collaboration with the Brain Research Centre, CDRD is providing key scientific and business expertise, state-of-the-art drug development infrastructure, and funding from its three Innovation Funds established with public and private sector strategic partners Genome BC, Pfizer Canada and Johnson & Johnson. This newly formed CDRD/BRC alliance will see further development of these projects, as well as a formalization of the relationship between the two organizations and additional future research collaborations going forward.
Research team discovers new type of spinal cord stem cell
A group led by a University of British Columbia and Vancouver Coastal Health scientist has discovered a type of spinal cord cell that could function as a stem cell, with the ability to regenerate portions of the central nervous system in people with spinal cord injuries, multiple sclerosis or amyotrophic lateral sclerosis (Lou Gehrig’s disease).
The radial glial cells, which are marked by long projections that can forge through brain tissue, had never previously been found in an adult spinal cord. Radial glia, which are instrumental in building the brain and spinal cord during an organism’s embryonic phase, vastly outnumber other potential stem cells in the spinal cord and are much more accessible. Their findings were published online this week in PLoS One.
Stem cells have the capability of dividing into more specialized types of cells, either during the growth of an organism or to help replenish other cells. Scientists consider stem cells a promising way to replace injured or diseased organs and tissues.
The search for spinal stem cells of the central nervous system has until now focused deep in the spinal cord. Jane Roskams, a professor in the UBC Dept. of Zoology, broadened the search by using genetic profiles of nervous system stem cells that were developed and made publicly accessible by the Allen Institute for Brain Science in Seattle.
Roskams, collaborating with researchers at the Allen Institute, McGill University and Yale University, found cells with similar genes – radial glial cells – along the outside edge of spinal cords of mice.
“That is exactly where you would want these cells to be if you want to activate them with drugs while minimizing secondary damage,” says Roskams, a member of ICORD (International Collaboration on Repair Discoveries) and the Brain Research Center, both partnerships of UBC and the Vancouver Coastal Health Research Institute.
Roskams’ team, including Wolf Tetzlaff, MD, PhD, also of ICORD and the BRC also found that radial glial cells in the spinal cord share a unique set of genes with other neural stem cells. Several of these – when mutated – can lead to human diseases, including some that target the nervous system. That discovery opens new possibilities for potential gene therapy treatments that would replace mutated, dysfunctional spinal cord cells with healthier ones produced by the radial glial cells.
“These long strands of radial glial cells amount to a potentially promising repair network that is perfectly situated to help people recover from spinal cord injuries or spinal disorders,” Roskams says. “For some reason, they aren’t re-activated very effectively in adulthood. The key is to find a way of stimulating them so they reprise their role of generating new neural cells when needed.”
The research was supported by the Canadian Institutes of Health Research, the Michael Smith Foundation for Health Research, the Natural Sciences and Engineering Research Council of Canada and the Jack Brown and Family Alzheimer’s Research Foundation.
Matthew Farrer appointed new BC Leadership Chair in Genetic Medicine
The University of British Columbia welcomes the appointment of Matthew Farrer as the new Dr. Donald Rix B.C. Leadership Chair in Genetic Medicine, the ninth B.C. Leadership Chair to be appointed at UBC.
Supported by $2.25 million from the Province of British Columbia through its Leading Edge Endowment Fund (LEEF), $2 million from LifeLabs and $250,000 from the Genome British Columbia Foundation, the chair is named for the late Dr. Don Rix, physician, philanthropist, and community and business leader.
Farrer and his research team will be based at the Department of Medical Genetics at UBC’s Faculty of Medicine, and at the Brain Research Centre (BRC) at UBC and Vancouver Coastal Health Research Institute. Farrer will also work with scientists at the Centre for Molecular Medicine and Therapeutics (CMMT). Led by Dr. Michael Hayden, CMMT played an instrumental role in the recruitment of the Chair.
The Chair was announced August 30 by Dr. Moira Stilwell, Parliamentary Secretary for Industry, Research and Innovation, at the Performance Arts Lodge (PAL) in downtown Vancouver. PAL is a community theatre venue where the Parkinson’s Society of B.C. holds one of its monthly patient support groups.
“Diseases of the brain are some of the greatest challenges facing medical science today, and funding this kind of cutting-edge research is a priority for our government,” said Stilwell. “Dr. Farrer will play a lead role in developing new drugs and therapies here in British Columbia for diseases that cause enormous suffering around the world for patients and their families.”
Stilwell was joined by John Hepburn, UBC Vice President Research and International, Mark Murphy, Director of LifeLabs Inc., Alan Winter, President of Genome BC Foundation, and Jim Smerdon, an early-onset Parkinson’s patient who was diagnosed four years ago, at age 32. Smerdon is one of an estimated 11,000 British Columbians – and 100,000 Canadians – with Parkinson’s disease.
“I am an optimist, which is one reason I put my heart and soul into raising money for Parkinson’s research,” said Smerdon, who is a member of Parkinson Society British Columbia. “Scientists like Dr. Farrer give me hope – for myself, and that someday people will never suffer the debilitating effects of Parkinson’s, because they will be diagnosed and treated first.”
An internationally renowned expert in the genetic aspects of Parkinson’s disease and related dementia, Farrer and his team have helped identify five genes involved in Parkinson’s by analyzing DNA from families in more than 20 countries on five continents.
His most recent discovery, published in the American Journal of Human Genetics last month, is the identification of a genetic mutation that causes late-onset Parkinson’s disease from DNA samples of a Swiss family where 11 relatives have developed the disease. This was the first Parkinson’s-related genetic discovery led by a Canadian team. Farrer and his team are now developing new therapies based on this and other genetic discoveries of the past decade.
“We are grateful to the Province of British Columbia for its continued support for research through the Leading Edge Endowment Fund,” said UBC Vice President John Hepburn. “I have no doubt that the high-calibre basic and translational research Dr. Farrer and his B.C. and international collaborators are carrying out right here in the province will have a tremendous impact on our understanding of – and ultimately help eradicate – Parkinson’s disease and other related debilitating brain disorders.”
“British Columbia has one of the most concentrated and high-calibre clusters of brain and neuroscience researchers, and one of the most robust biotech industries in the world,” said Farrer, who also holds the Canada Excellence Research Chair in Neurogenetics and Translational Neuroscience at UBC. “This synergy provides the perfect environment for me and my team to make fundamental genetic discoveries and translate them into treatments that will improve the quality of life for patients suffering from neurodegenerative diseases and that of their families.”
“We are delighted to have this research chair named in honour of Dr. Rix in recognition of his many years of exemplary leadership in British Columbia’s biotechnology and medical research sectors,” said LifeLabs’ Mark Murphy. “We hope our support of Dr. Farrer’s innovative research will help reduce the burden that neurodegenerative diseases have on our health-care system and, most importantly, on families.”
“Genome BC is pleased to be able to bring together private industry, academia and government to harness new opportunities for health research,” said Genome BC President Alan Winter. “The appointment of Dr. Farrer to the Dr. Donald Rix B.C. Leadership Chair in Genetic Medicine will allow us to continue to build upon the great foundation in brain research in B.C. and contribute to new and improved treatments for patients everywhere.”
Parkinson’s disease is the second most common chronic neurodegenerative disorder after Alzheimer’s. It is estimated that 10 million Canadians – nearly one-third of Canada’s population – will be affected by brain disease, disorder or injuries at some time in their lives. The financial burden of treating these conditions is estimated to cost the Canadian healthcare systems $30 billion annually.
“Genetic research is helping us uncover previously unknown connections among rare and more common brain diseases, and this new knowledge is helping us better understand how the brain reacts to – and even repairs itself from – diseases and injuries,” said Brain Research Centre Director Max Cynader. “Dr. Farrer’s work, taken with ongoing research at the BRC, will bring us even closer to unravelling the mysteries of our brain.”
“Since joining UBC a year ago, Dr. Farrer has already made his mark by releasing the first Canadian-led discovery of a Parkinson’s-related gene mutation – and is about to publish another,” said Dr. Gavin Stuart, dean of the Faculty of Medicine and UBC’s Vice Provost Health. “He is a tireless supporter of patient-centred science – an area UBC is well-known for – and that is especially good news for the people of British Columbia.”
“The LEEF Chair came to fruition as a result of CMMT and UBC’s invaluable partnership with Genome BC and LifeLabs,” said CMMT Director Dr. Michael Hayden. “The award in Don Rix’s name in Genetic Medicine is particularly significant as it recognizes Don’s visionary leadership and commitment to the translation of genetic knowledge to society. Don was a wonderful mentor, friend, and an inspiration to me and countless others.”
Newly identified gene mutation linked to Parkinson’s disease
A team of researchers led by Dr. Matthew Farrer has identified a genetic mutation that causes late-onset Parkinson’s disease, paving the way to a new target for potential treatments that may halt or cure the debilitating neurodegenerative disease.
The mutation, located on a gene called VPS35, was identified using a novel technology called exome sequencing, which allowed scientists to reveal all gene mutations from an individual. Details of the study were published July 14 in The American Journal of Human Genetics.
“We applied this technology to DNA samples from two cousins diagnosed with Parkinson’s disease. They are part of a Swiss family where eleven people have developed the disease,” says lead author Dr. Carles Vilariño-Güell, a post-doctoral research associate in UBC’s Dept. of Medical Genetics and a member of the Centre for Molecular Medicine & Therapeutics (CMMT).
“We found one previously unidentified mutation was present in all the individuals in this family who had developed Parkinson’s disease, but we did not see this mutation in any of the more than 3,000 healthy individuals whose DNA samples we studied,” says Dr. Vilariño-Güell.
He and senior author Dr. Farrer subsequently found the VPS35 mutation in eight more patients with Parkinson’s disease from three other families, and one patient with no family history of disease. The families originated in countries as geographically disparate as Tunisia and the United States.
“This conclusively proves that this mutation is the cause of disease in these patients,” says Dr. Vilariño-Güell.
Dr. Farrer, a professor in the Dept. of Medical Genetics and Canada Excellence Research Chair in Neurogenetics and Translational Neuroscience at UBC, says the identification of the VPS35 mutation provides new clues for understanding the pathological mechanisms that lead to Parkinson’s disease. VPS35 is a critical component of a protein recycling system in neurons, called the retromer. Deficiencies in the retromer system have previously been linked to Alzheimer’s disease and other neurological conditions such as Charcot-Marie-Tooth.
“Our findings show, for the first time, that the retromer system is also an important mechanism for Parkinson’s – and perhaps other neurological disorders,” says Dr. Farrer, who’s also a senior scientist at CMMT and a member of the Brain Research Centre at UBC and Vancouver Coastal Health Research Institute.
Prior discoveries have identified mutations in five genes that predispose people to developing Parkinson’s.
“This new finding provides another piece of the Parkinson’s puzzle that will allow us to investigate what’s going on in the brains of people with Parkinson’s – and to work towards developing and testing novel therapies to halt, treat, and potentially cure this terrible disease,” says Dr. Farrer, who joined UBC from the Mayo Clinic in Jacksonville, Florida last year.
More than 100,000 Canadians, approximately one million Americans and more than 10 million people worldwide are affected by Parkinson’s disease. Symptoms include trembling in hands, arms, legs, and face, stiffness in the limbs and torso, as well as slow movement and poor balance and coordination. There is currently no cure and most treatments only tackle the symptoms.
Dr. Vilariño-Güell first presented the discovery in March at the International Alzheimer’s disease and Parkinson’s disease congress in Barcelona. He was awarded the Greenberg Family Award, which is given to talented young scientists with the intent of advancing their research into the diagnosis and treatment of Parkinson’s disease.
Researchers throughout the world are now checking their genetic samples based on Dr. Farrer and Dr. Vilariño-Güell’s findings as they pursue a deeper understanding of the biological processes triggered by the VPS35 mutation that result in the development of Parkinson’s disease. Press coverage has been extensive, including news outlets in the US, the UK, and Asia.
The research was supported by the Michael J. Fox Foundation, the Parkinson’s Disease Foundation, and the Canada Excellence Research Chairs program.
Pregnancy outcomes in women with MS: study offers reassurance
Women with MS are as likely to deliver healthy babies as women who don’t have MS, according to new research by the University of British Columbia and Vancouver Coastal Health Research Institute.
Researcher Mia van der Kop analyzed 432 births to women with MS and nearly 3,000 births to women without MS in British Columbia between 1998 and 2009. She found no significant differences in the timing of delivery, or birth weight between babies born to women with or without MS.
“Other studies have shown MS was associated with poor outcomes,” says senior author Helen Tremlett, Associate Professor in the Faculty of Medicine’s Division of Neurology, and Canada Research Chair in Neuroepidemiology and Multiple Sclerosis. “Our finding that MS was not associated with poor pregnancy or birth outcomes. That should be reassuring to women with MS who are planning to start a family.”
In their study, Tremlett and first author Mia van der Kop, an epidemiologist with the MS group, found babies born to women with MS did not have significantly different gestational ages or birth weights compared to babies born to women who don’t have MS. Rates of caesarean section and vaginal births were also generally comparable.
Age at onset of MS, and the duration of disease were not linked to adverse delivery or neonatal outcomes, although there was a hint that women with higher levels of disability might be at a slightly higher risk of c-section or assisted vaginal birth. In both cases, findings were not statistically significant, and require further investigation, according to van der Kop.
“There’s a trend in our data,” reflects Dr. Tremlett, a member of the Brain Research Centre. “Other researchers should see if they can verify what we found.”
“The importance of body mass index and pregnancy-related outcomes in MS should also be explored in future studies,” van der Kop adds. Women with MS were more likely to be overweight or obese, which is associated with greater risk during pregnancy and childbirth.
Multiple sclerosis is considered an auto-immune disease that attacks the protective covering – known as myelin – of the brain and spinal cord. This causes inflammation and often destruction of the myelin sheath. Symptoms include numbness or tingling in the hands and feet, feeling off-balance, clumsiness and visual and cognitive problems. In severe cases, it can lead to paralysis and blindness.
Dr. Tremlett and van der Kop attribute their nuanced findings to the quality of the data they were able to access for their study. They used data from the British Columbia MS Clinic’s database, combined with records from BC’s Perinatal Database Registry. “It’s really rich data,” remarks Dr. Tremlett, “it provides information about MS disability and disease duration, drug exposure as well as pregnancy outcomes. The data is collected in real time, at the clinic or at the time of birth, so we’re not asking people what happened months or years later, as some studies have to.”
All participants included in the study were diagnosed with MS by a neurologist, which has not been the case in previous research. For example, a recent US study used women whose MS was recorded in hospital records. “That wouldn’t pick up the broad spectrum of patients that our study was able to,” says Dr. Tremlett.
“I believe our results are generalizable to other populations in Canada and the US,” she adds. An estimated 55 to 75,000 Canadians have been diagnosed with MS, while as many as 400,000 Americans are thought to have the disease.
Future Directions
Dr. Tremlett and van der Kop’s pregnancy outcomes study is one of four parts of a Canadian Institutes of Health Research (CIHR)-funded program that will examine multiple aspects of pregnancy and pregnancy outcomes in women and families with MS. A study looking at the impact of drugs used to treat MS on pregnancy outcomes is already underway, and members of Dr Tremlett’s team plan to also examine the impact of fathers with MS undergoing drug treatment at the time of conception.
“The focus is typically on the woman around the time of conception and pregnancy, with the role of the father often overlooked,” says Tremlett. “However, there is increasing awareness that the health and drug exposure of the would-be-father at the time of conception could well be important. It can be a difficult area to study, but we want to see if it’s feasible or not in MS. We’re also interested in looking at longer-term outcomes in children where the mother or father has MS,” she adds.
CIHR funding will cover the pregnancy-outcomes research, and further funding is being sought to look at longer-term outcomes in children with a parent with MS. Dr. Tremlett expects the CIHR-funded studies will be completed in 2012, offering for the first time a comprehensive picture of the MS pregnancy experience.
Other members of the UBC team involved with this research were Drs. Leanne Dahlgren; Anne Synnes; Dessa Sadovnick and Ana-Luiza Sayao as well as Mark Pearce from Newcastle University, UK.
New levels of resiliency found in post-stroke brain
Immediately after a stroke, the brain begins compensating for loss of function in one hemisphere with increased activity in other parts of the brain, according to new research by the University of British Columbia and Vancouver Coastal Health.
A team led by neuroscientist Timothy H. Murphy found that as soon as half an hour after a stroke, the brain begins to reorganize – recruiting existing pathways within the undamaged hemisphere to perform functions compromised by lack of blood flow or ruptured vessels in the damaged areas of the brain.
“Our study reveals this underlying resilience in the brain, and examines the mechanisms that bring about these changes after a stroke,” says Dr. Murphy, a Professor in the Department of Psychiatry and a scientist at the Brain Research Centre at Vancouver Coastal Health and the University of British Columbia.
Murphy’s team induced mini strokes in mice, and then monitored sensory activity in their brains for as long as two hours while stimulating the animals' forepaws. “We found that when the stroke occurred in the left hemisphere–which controls the right paw–sensory activity was higher in the right hemisphere, whether we stimulated the left or the right paw, compared to sensory activity prior to stroke,” says Dr. Majid H. Mohajerani, lead author of the study, and member of Dr. Murphy’s laboratory. The team also observed that at the same time, the brain diverts more resources to the undamaged front limb, enhancing its potential strength and capacity.
Rewiring in the brain typically occurs in the months following stroke. “The changes we observed came too soon to have resulted from circuit rewiring.” Mohajerani adds. “Our research suggests that stroke activates unique synaptic signals. These signals remove an inhibition that acts as a block on existing parallel pathways in the undamaged hemisphere of the brain that continue to function, despite the effects of stroke.”
Murphy and his colleagues’ research reinforces other emerging evidence that suggests the brain utilizes its undamaged, mirror side in stroke recovery. “The widespread changes in activity we observed occurred too rapidly after a stroke to involve new neural connections,” says Mohajerani. “That does not rule out the possibility that structural circuitry formed over a longer period of time also plays a role in stroke recovery, but our work supports new thinking about how the brain engages in that process.”
The study, published online in the early edition of Proceedings of the National Academy of Sciences May 16, is drawing international interest from other prestigious scientific journals, including Nature.
Support for this research came from awards from the Canadian Institutes of Health Research, Michael Smith Foundation for Health Research, the Human Frontier Science Program, the Heart and Stroke Foundation of Canada and the Heart and Stroke Foundation of British Columbia and Yukon.
Three eminent awards recognize Dr. Michael Hayden's Research
Internationally known for his genetic research, Brain Research Centre member Dr. Michael Hayden was recently honoured with three prestigious awards acknowledging his outstanding leadership in medical genetics, entrepreneurship, and humanitarianism.
A Killam professor in UBC’s Department of Medical Genetics and director and senior scientist at the Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, Dr. Hayden won the 2011 Margolese National Brain Disorders Prize in late April, as well as the Canada Gairdner Wightman Award, and the Killam Prize in health sciences conferred by the Canadian Council for the Arts, both in March.
Seminal Discoveries
“Dr. Hayden’s seminal discoveries, the translational aspect of his work, and his prolific research have established him as one of the world’s leading authorities on Huntington Disease,” said Alison Buchan, Vice Dean, Research and International Relations at the University of Toronto’s Faculty of Medicine, who also chaired the Margolese Prize impact and review panel. ”He shows no signs of letting up in unraveling the mechanisms of Huntington disease, as well as applying his insights to other neurodegenerative conditions, such as Alzheimer’s disease,” she added.
A rare individual whose life’s work has bridged theory and practice, Dr. Hayden has furthered understanding of the genetic cause of illness in search of better treatments for neurodegenerative disorders–especially Huntington disease (HD)–which cause uncontrolled movements, loss of intellectual faculties, and emotional disturbance. He is the world’s most-cited author on HD, with more than 600 peer-reviewed publications and invited submissions. He developed a predictive genetic test for the condition, which is now the standard of care worldwide.
His later research has contributed much to our understanding and identification of atherosclerosis, HD and inherited lipid disorders, in which harmful amounts of fatty materials called lipids accumulate in the body. Dr. Hayden and his research group have identified 10 disease-causing genes, including ABCA1, which has major implications for atherosclerosis and diabetes. Dr. Hayden also identified the first mutations underlying Lipoprotein Lipase (LPL) Deficiency and developed gene therapy approaches to treat this condition.
Dr. Hayden is the founder of three successful biotechnology companies, including Aspreva Pharmaceuticals Inc. that tests existing medications as potential treatments for “orphan” diseases so rare, they are often overlooked by the medical and research communities. He is also involved in an international fundraising effort for a community centre for HIV/AIDS-affected children in his native South Africa.
The Margolese National Brain Disorders Prize recognizes Dr. Hayden’s outstanding contributions as a Canadian to the treatment, amelioration or cure of brain disorders. The annual prize, bestowed by UBC, is awarded to a UBC faculty member only once every six years.
The Canada Gairdner Wightman Award recognizes Dr. Hayden as one of the world’s leading scientists, whose research contributes significantly to the conquest of disease and relief of human suffering. The Gairdner Award celebrates excellence in the realm of health sciences, particularly leadership in medicine and medical science.
The Killam Prize in Health Sciences recognizes career achievements in the health sciences. In awarding Dr. Hayden one of five prizes, the Canada Council highlighted Dr. Hayden’s qualities as a humanitarian, and his willingness to take risks when confronted with patients once left to wonder if they too might be affected by a genetic disease.
How neurons die in Down Syndrome and Alzheimer's Disease
Weihong Song, a Professor in the Department of Psychiatry and a member of the Brain Research Centre, uncovered the same mechanism that leads to brain cell destruction in people with either condition.
Read more about this story here.
Uniting research with patient care: Dementia 2011 forum
The VCH Clinic for Alzheimer’s disease and Related Disorders at UBC Hospital (CARD-UBCH) provides comprehensive clinical assessment and treatment for patients and conducts important educational and research initiatives directed at understanding causes and treatments of dementia.
Each year, patients, staff, and the public can participate in an important forum organized by CARD-UBCH in order to gain a greater understanding of the science of dementia and living with dementia. This year, Dementia 2011 features 12 VCH researchers and clinicians covering leading-edge aspects of Alzheimer’s disease and related conditions. Topics include advances in early diagnosis and treatment options, and meaningful activities for people living with dementia. It also includes the very latest research, such as Cheryl Wellington’s (photo above, credit: Brian Smith) work examining the link between Alzheimer’s disease and cholesterol.
Did you know? The VCH Clinic for Alzheimer disease and Related Disorders:
- Is the most comprehensive and only clinic of its kind in BC and serves over 1000 patients a year from across the province
- Takes a multidisciplinary approach to assessing patients. Overall health is reviewed in detail
- Provides patients with the opportunity to participate in clinical trials research
Dementia 2011
Date: Saturday January 29, 2011
Time: 8:50 a.m. to 12:30 p.m.
Location: UBC -- Life Sciences Center, Rooms LSC 1 and 2 (2350 Health Sciences Mall)
Registration Deadline: January 28 (8:00 p.m.)
Refreshments provided. Patients, family members, caregivers, friends, and other members of the public are invited to attend.
Research activity at Vancouver Coastal Health is supported by Vancouver Coastal Health Research Institute and our academic partner, University of British Columbia.
"Mini-strokes" may pose a bigger threat than previously thought
A team led by Lara Boyd found that transient ischemic attacks might not be transient after all, but could inflict lasting damage on the brain. Read more about this story here.
Photo credit: Lisa Grixti, Heart & Stroke Foundation of BC & Yukon
Premier Campbell visits the Brain Research Centre
The Premier opened a conference sponsored by the Canadian Dementia Action Network and the Brain Research Centre. Read more about this event here.
Photo credit: UBC Faculty of Medicine
Collaboration in imaging and neurobiology leads to understanding of mechanisms of an inheritable form of migraine
Success in brain research is often measured in small increments: discovering a gene mutation that causes a disease, finding out the mechanism of that mutation, determining related disease pathways, and understanding inter-related cellular and molecular mechanisms.
But each step—each seemingly small victory—adds more valuable information that not only helps us understand the causes and mechanisms of brain disorders, but builds a solid foundation upon which to devise strategies for managing, treating, and preventing these disorders.
The Brain Research Centre, a partnership of the UBC Faculty of Medicine and Vancouver Coastal Health Research Institute, is home to faculty with expertise in a broad spectrum of areas and investigative techniques. One of the strengths of the Centre is our collaborative working environment: opportunity abounds for experts in imaging, for example, to come together with experts in molecular neurobiology.
Brian MacVicar (left, in photo), a Professor in the Department of Psychiatry, is one such expert in imaging whose collaborations with Terry Snutch (right, in photo), a Professor in the Michael Smith Laboratories and Departments of Zoology and Psychiatry, and an expert in molecular neurobiology, have resulted in greater understanding about the cellular and molecular mechanisms underlying an inheritable form of migraine headache.
Familial Hemiplegic Migraine (FHM) is a type of inheritable migraine that includes debilitating weakness of significant portions of the body during the aura phase, in addition to visual or other sensory disturbances. FHM is caused by mutations in the genes that code for certain ion channels—the conduits by which compounds like calcium, potassium, and sodium, enter and exit brain cells for normal brain functioning. Ion channels are located in the synapses of brain cells—the points of connection between cells.
There are several sub-types of FHM, depending on which ion channel is affected by the mutations. Drs. MacVicar and Snutch investigated the molecular mechanisms underlying FHM-1, which is caused by mutations to the genes that code for a particular type of calcium ion channel. The results were published in the Proceedings of the National Academy of Sciences in October 2010. Paul Adams, a student with Dr. Snutch, and Ravi Rungta, a student with Dr. MacVicar, are first authors on the paper.
They found that in mouse models the FHM-1 mutation leads to more active calcium channels, allowing for greater than normal amounts of calcium to enter brain cells. In healthy individuals, the amount of calcium entering brain cells increases or decreases based on brain activity. However, in individuals with FHM-1, because the calcium channels are always in a high state of activity, this leads to higher concentration of calcium and stronger synaptic connections between neurons. This high resting level of activity is thought to reduce the threshold for brain activity to trigger the migraines.
While Drs. MacVicar and Snutch have determined how the FHM-1 mutation translates into cellular and molecular dysfunction and how this mutation increases susceptibility for the migraines, further work is needed to link this work to what specifically triggers a migraine in the first place. Individuals with FHM-1 don’t typically suffer from non-stop migraines, and are instead significantly more prone to developing them in response to certain triggers such as stress or head injury. Dr. MacVicar is now investigating this link further, and Dr. Snutch is looking for related or associated pathways that could be potential targets for treatment.
Photo caption: Live nerve cells stained with fluorescent dye for measuring activity. Credit: Ravi Rungta
Brain Research Centre home to division of new global virus research network
At a meeting held March 1-3, 2011 in Washington, DC, top medical virologists representing more than a dozen countries ratified their participation in and support of the newly-formed Global Virus Network (GVN), a global authority and resource for the identification, investigation, and control of viral diseases posing threats to humankind. The Brain Research Centre, a partnership of the UBC Faculty of Medicine and Vancouver Coastal Health Research Institute, will be home to the neurovirology division of this international network.
Under the leadership of Professor Max Cynader, Director of the Brain Research Centre, and Professor Chris Tan, UBC Division of Neurology, the Vancouver research team will investigate emerging viruses and virus-like infectious agents that affect the brain.
“Global health this century will be most challenging because of a complex combination of factors including urbanization, high population density, changing demographics, and environmental factors,” said Professor Tan. “It is inevitable that this will lead to the genesis of new epidemics, requiring the world community of scientists to urgently come together to prepare for the next pandemic of new and unknown diseases. We are delighted to become a part of this international effort to address these global health threats.”
Other members of the local team include Dr. Neil Cashman, UBC Division of Neurology, Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases, and Director of the ALS Clinic at G.F. Strong Rehabilitation Hospital; Professor William Jia, UBC Department of Surgery; and Dr. Joe Kates, Chief Scientific Officer of Calidris Therapeutics Ltd.
The GVN fulfills a goal of Dr. Robert C. Gallo, the GVN co-founder and Director of the Institute of Human Virology at the University of Maryland School of Medicine, and who’s widely known for his discovery of the first human retroviruses (including one which causes a specific kind of leukemia), his co-discovery of HIV, and the development of the HIV blood test. Since the early 1980’s and following the immediate HIV/AIDS outbreak, Dr. Gallo began promoting the need for global collaboration to overcome gaps in research during the earliest phases of viral epidemics and to ensure that sufficient numbers of medical virologists are trained to meet these challenges.
In addition to identifying new and emerging viruses, the goals of the GVN include creating an international network of virus experts, building collaborative research alliances within the network, training future generations of virus researchers, and public health education regarding new and emerging viruses.
About the Global Virus Network (GVN)
The Global Virus Network (GVN) is an independent organization comprised of leading medical virologists from Argentina, Australia, Canada, China, Germany, India, Ireland, Israel, Italy, Pacific Rim Consortium (Japan, Korea, and Hong Kong through the A-IMBN), Russia (in collaboration with Azerbaijan, Belarus, Estonia, Georgia, Latvia, Lithuania, Uzbekistan, and Ukraine), South Africa, Spain, Sweden, the United Kingdom, and the United States of America. The GVN will be a global authority and resource for the identification, investigation, and eradication of viral diseases that pose threats to mankind. The GVN enhances the international capacity for reactive, proactive and interactive activities that address mankind-threatening viruses. The GVN addresses a global need for coordinated virology training, developing scholarly exchange programs for recruiting and training young scientists in medical virology. The GVN will serve as a resource to governments and international organizations seeking advice about viral disease threats, prevention or response strategies. The GVN will advocate research and training on virus infections and their many disease manifestations, and will act as a clearinghouse for the dissemination of information to authorities, scientific communities and the world publics.
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Over-the-counter anti-inflammatory drugs may help prevent Alzheimer's Disease in populations with no family history of the disease
Weihong Song, a Professor in the UBC Department of Psychiatry and a member of the Brain Research Centre at UBC Hospital, has uncovered a potentially “vicious cell cycle” by which Alzheimer’s plaque formation is perpetuated in sporadic cases of the disease—and a possible treatment.
By examining the post-mortem brain tissues of 18 patients with Alzheimer’s Disease and 13 healthy controls, Dr. Song discovered that the patients with Alzheimer’s Disease had elevated levels of two protein products called BACE1 and NF-κB.
BACE1 is an enzyme that behaves similar to a pair of scissors, cutting a specific protein into smaller protein pieces called amyloid beta. It is the accumulation of amyloid beta in the brain that characterizes Alzheimer’s Disease. NF-κB is a protein that is implicated in inflammation, oxidative stress, and cell death. It is also involved in regulating the production of proteins. In 2006, Dr. Song discovered that the production of BACE1 is very tightly controlled and that elevated BACE1 activity is implicated in the development of Alzheimer’s Disease and dementia in Down Syndrome.
Based on these observations and research, Dr. Song used cell culture techniques to discover that NF-κB not only physically interacts with the genes that produce BACE1, but also regulates the production of BACE1. In doing so, he discovered a potentially “vicious cell cycle.”
“Abnormal accumulation of amyloid beta protein, which occurs in Alzheimer’s Disease, causes oxidative stress and inflammation in the brain,” said Dr. Song, who is also a Canada Research Chair in Alzheimer’s Disease and Director of the Townsend Family Laboratories in UBC Hospital. “This inflammation activates more NF-κB, which increases the activity of BACE1 and causes more amyloid beta protein to accumulate in the brain. The cycle just continues to repeat itself.”
Because NF-κB is implicated in inflammation, Dr. Song hypothesized that giving over-the-counter anti-inflammatory drugs such as aspirin or ibuprofen might halt this vicious cycle.
The results, which were published online in the February edition of the International Journal of Neuropsychopharmacology, suggest that using anti-inflammatory drugs to inhibit the activity of NF- κB could be a valuable target for developing novel drug therapies for sporadic cases of Alzheimer’s Disease.
However, further work is needed to investigate these results.
“While these results are promising,” said Dr. Song, “we still need to determine appropriate dosing and frequency, as well as determining which anti-inflammatory drugs are most safe and efficient. We also need to determine the specific cellular pathways that are responsible for increased NF-κB activity in Alzheimer’s Disease.”
This research was supported by the Canadian Institutes of Health Research, Jack Brown and Family Alzheimer’s Research Foundation, and the Michael Smith Foundation for Health Research.
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