Making Headway
by Mind Over Matter V 14:
Expansion Grants Help Ensure Research Equity
Women’s Brain Health Initiative’s signature fundraising event, the Stand Ahead® Challenge, is delivering on its mission to stand up against research bias and to stand ahead for women’s brain health, raising funds for essential research that considers sex and gender differences to combat brain-aging diseases that disproportionately affect women.
The annual December 2nd event, celebrated on Women’s Brain Health Day, raises awareness for research inequity, encourages contributions for research that better meets women’s needs, and inspires participation in a fun viral challenge – such as performing a headstand, playing a card memory game, or signing your name with your non-dominant hand. Thousands of people have taken part in the Stand Ahead® Challenge and, most importantly, donated. In its first three years, the Stand Ahead® Challenge has raised over $2,000,000, including a crucial boost from The Citrine Foundation of Canada and generous support from Brain Canada, which has matched donations up to $250,000 each year.
Now, those donations are supporting vital new research that incorporates sex and/or gender considerations.
Women’s Brain Health Initiative (WBHI) is collaborating with Brain Canada and the Canadian Institutes of Health Research (CIHR) to fund a project led by Dr. Mario Masellis, an Associate Professor in the Department of Medicine at the University of Toronto. This intriguing project is part of a prestigious international initiative, the European Union Joint Programme on Neurodegenerative Disease (JPND).
Working with researchers in the Netherlands, Italy, Sweden, and the Czech Republic, Dr. Masellis will examine the interplay between an individual’s genetic, cardiovascular, and demographic background (including sex, age, and education) in order to determine how they may interact to increase the risk of developing dementia and/or worsen how dementia is presented. Dr. Masellis and his team will also explore the use of novel methods to unravel the underlying causes of dementia in late life.
While Alzheimer’s disease is the most common cause of dementia, many people may also have concomitant Lewy body pathology, frontotemporal dementia pathology, and/or cerebrovascular disease, which also contributes to the clinical manifestations of dementia. Currently, it takes an autopsy to determine whether an individual has a so-called “pure” form of one of those conditions or a mixture of different diseases.
Dr. Masellis and his colleagues are trying to discover a way of accurately diagnosing people while they are still alive.
“This is really important to know,” said Dr. Masellis, who is also a clinician-scientist with the Sunnybrook Research Institute. He told Mind Over Matter® that one reason that dementia drug trials have failed is because they may be targeting one particular condition in a person who may in fact have a mixture.
“If we can come up with a better way of diagnosing an individual in life with the actual brain pathologies causing their dementia presentation, then we may have a better success story in developing and identifying new drugs.”
The researchers will be assessing data from more than 3,000 individuals with dementia in both Canada and Europe. The information will be cross-referenced with a large cohort of 15,000 participants from the Rotterdam Study in the Netherlands, which involves older adults living in the community who have not yet exhibited any signs of cognitive decline.
The researchers want to determine whether they can not only predict the onset of dementia, but also whether it is due to a singular pathology or a combination. An accurate, early diagnosis of dementia offers the hope of targeted treatments that could delay or even stop cognitive decline.
The funding from WBHI, Brain Canada, and CIHR, coupled with support from JPND, means that the project has a budget in excess of CDN$1.4 million.
“Without their support, we would not be able to answer these challenging questions. The funding contribution from Canada is going to make a difference in the global battle against dementia,” noted Dr. Masellis.
Money raised through the Stand Ahead® Challenge is also giving a boost to several researchers who had already received funding, allowing them to further build on their work. Six exceptional research teams have been selected to receive a funding boost of $105,000 each through a new initiative, the Brain Canada-WBHI Expansion Grants: Considering Sex and Gender Program. The goal of the program is to support researchers who want to explore the role that sex and gender play in aging, neurodegenerative disorders, and stroke by implementing sex- and gender-based analysis (SGBA)-driven research hypotheses into their current work.
“Research approaches that consistently account for sex and gender differences drive innovation and scientific rigour,” said Dr. Viviane Poupon, President and CEO of Brain Canada Foundation.
“Our role is to enable high-impact research and reduce gender-based health inequities for previously silenced voices. Brain Canada introduces sex, gender, and diversity considerations at every stage of the granting process. We emphasize its importance in the research hypotheses and in doing so we contribute to broadening the potential impact of the work and the potential for new knowledge to be translated into health benefits. We want to help everyone improve their brain health and quality of life, so we must include everyone in the research.”
“These kinds of research projects go to the heart of our mission,” added WBHI Founder and President Lynn Posluns. “We’re so pleased to be able to tell the people who donated to the Stand Ahead® Challenge that their contributions are going to support such critical work.”
“This was very timely and wonderful, and I’m really pleased to see Brain Canada and WBHI supporting this type of research,” said Dr. Jodi Edwards, one of the first recipients of the expansion grant. Dr. Edwards is the Director of the Brain and Heart Nexus Research Program at the University of Ottawa Heart Institute (UOHI).
She and her team have been exploring the use of non-invasive brain stimulation to assist stroke patients in recovery. Transcranial magnetic stimulation (a form of brain stimulation that uses an electromagnetic coil placed over the scalp to stimulate brain cells) is a treatment that has been used in depression, but also shows great promise in helping the brain to repair the damage caused by stroke. However, exploring its potential for stroke recovery requires large and complex clinical trials.
Dr. Edwards and her colleagues are building a platform for those trials, which they are calling “CanStim,” short for the “Canadian Platform for Trials in Non-Invasive Brain Stimulation” – an initiative that has already drawn interest from researchers in the U.S. and Europe who are interested in using this platform for their own projects.
Crucially, the expansion grants will allow the researchers to embed sex and gender analysis into their work from the outset of the trial design.
Women may have a higher risk of stroke than men and suffer more damaging long-term consequences, including being more likely to require long-term care. It is critical to develop new tools to optimize recovery for all stroke patients, and women especially, in order to enable people to live independently in aging.
“This funding is an exciting opportunity to explore these differences and it is so important that WBHI and Brain Canada have recognized that women and men have different recovery mechanisms and trajectories, and that sex should be considered in this research,” Dr. Edwards told Mind Over Matter®.
Dr. Christian Éthier is exploring a different form of potential therapy for stroke recovery. The Associate Professor in the University of Laval’s Department of Psychiatry and Neurosciences is exploring the role of dopamine, a chemical in the brain often associated with pleasure. Using laboratory rats, Dr. Éthier is studying whether stimulating the release of dopamine can assist in repairing a brain damaged by stroke.
“Our experiments are really fundamental. We’re trying to understand the principles by which motor recovery occurs,” he said. Dr. Éthier is using the expansion grant to explore the differences between females and males.
Dopamine could be more important for females, which would inform the development of appropriate therapies.
“For me, the expansion grant is very significant because this allowed me to explore something new – to explore untested territory,” Dr. Éthier told Mind Over Matter®.
Dr. Mark Bayley, Program Medical Director and Psychiatrist in Chief at Toronto’s University Health Network-Toronto Rehabilitation Institute, along with the team from the CanStroke Recovery Trials Platform, is investigating a global issue with implications that resonate beyond stroke research: the challenge in recruiting an equal number of women and men to participate in clinical studies.
Although women make up the majority of stroke patients, they sometimes represent only 20% to 30% of the participants in studies.
“This has been recognized as a worldwide problem in research. The evidence for most care may be fundamentally flawed because of the under-recruitment of women in research. We’d like to understand why,” said Dr. Bayley, who is also a scientist with the Canadian Partnership for Stroke Recovery.
His expansion grant will be used to investigate the reasons behind the sex disparity and to identify tactics for improving female participation.
Led by colleagues Dr. Shannon MacDonald of Toronto’s Sinai Health System, Dr. Susan Marzolini of University Health Network (UHN) in Toronto, Dr. Amy Yu of Sunnybrook Hospital, and Dr. Janice Eng of University of British Columbia, the project will survey up to 200 individuals who had previously participated in research projects, with the goal of discovering what made it easier to take part in the study and what made it more challenging.
The research team has their suspicions as to why women turn out in lower numbers, including issues with the recruitment approach, caregiving responsibilities, lack of transportation, and/or insufficient support from a life partner. The researchers are seeking to provide specific information that can inform the development of a best practices guide to improve female participation.
“We’re very grateful for this funding. It will help us build a foundation of science based on the whole of the human population. The results of this research might actually inform not just Canadian stroke recovery research but other research we do in Canada in many other fields,” said Dr. Bayley.
For Dr. Janelle Drouin-Ouellet, funding from Brain Canada has been crucial in launching her career and now the expansion grant is allowing her to further develop her work. An Assistant Professor at the University of Montreal’s Faculty of Pharmacy, Dr. Drouin-Ouellet previously received a Future Leaders in Canadian Brain Research grant aimed at early career researchers, which enabled her to embark on a project exploring Parkinson’s disease. Her work uses an innovative technique that involves converting skin cells from seniors into microglia, which are the immune cells in the brain that are affected by Parkinson’s.
Dr. Drouin-Ouellet mimics the effects of Parkinson’s disease on those cells in a petri dish, and studies how they react to different treatments. The latest funding will allow her to explore sex differences.
Men develop Parkinson’s disease more frequently than women and we need to increase our understanding as to why this is the case.
“Once we understand the biology, the mechanisms underlying this, then we can perhaps look for sex-specific therapies,” said Dr. Drouin-Ouellet.
She will study how female and male microglia react differently to the stresses of the disease and will endeavour to treat male cells with female hormones and female cells with male hormones to see if this has a beneficial or negative effect. It is a line of research made possible by the new round of funding.
“As a young principal investigator, this is tremendously helpful. It allows me to build on what we’ve done so far,” she said.
Dr. Jonathan Epp, Assistant Professor in the Department of Cell Biology and Anatomy at the University of Calgary, also benefited from an early career grant from Brain Canada, which allowed him to pursue a project that he believes other funding bodies might have viewed as too high risk. Using mice, he is exploring potential interventions that could reduce cognitive decline in individuals with Alzheimer’s disease (AD), focusing on how different parts of the brain communicate with each other.
In women with AD, cognition tends to deteriorate more rapidly than men, potentially in part because there is a greater disruption in certain brain neurons.
Dr. Epp has been exploring whether the cognitive deterioration can be slowed by housing mice in an environment with more stimulation, including more opportunities for exercise. With the expansion grant, he is broadening his explorations by using cutting-edge techniques such as optogenetics and chemogenetics to study their impact on brain neurons. Optogenetics is a way of stimulating neurons through the application of light, while chemogenetics uses drugs to achieve a similar purpose.
“The most important thing from a therapeutic point of view is to find the correct targets to go after, and that’s what we’re interested in the mouse models,” explained Dr. Epp. A central element of his project will involve studying how the stimulation affects females and males differently.
“I was really excited to see this expansion grant focusing on sex differences. To me, it’s a very important area of research because there’s so much there that we don’t know because a lot of the past work has just been done in male. Sometimes that completely washes out the effects.”
Even less is known about the subject that Dr. Gillian Einstein’s team is exploring – the effect of long-term hormone therapy on the cognition of trans women.
“From a human point of view, from the perspective of what is just, this group deserves to have more known about their physiology and their brain health so that ultimately we can have precision medicine for this group of people as well,” said Dr. Einstein, who, with support from WBHI and CIHR, holds the Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging at the University of Toronto, the first research chair of its kind in the world.
She also feels that it is essential to have a trans woman playing a central role as a researcher in the project. Reubs Walsh, a British researcher, is relocating to Toronto and will lead the study as a postdoctoral fellow. Walsh has received postdoctoral funding from WBHI, The Citrine Foundation of Canada, and the University of Toronto Arts and Science Postdoctoral Fellowship.
“We know from the literature on post-menopausal aging in cis women that hormone therapy is controversial. So, we want to understand how it might affect cognition in this population of women. There’s been very minimal research in this area,” said Dr. Einstein.
The initial funding from Brain Canada launched the project and now the expansion grant will allow her team to include brain imaging, detailed interviews, and in-person cognitive testing. The research also plans to measure cortisol (the stress hormone) to better understand the impact of stress, which is a common challenge among trans people.
“I’m so excited about this project,” said Dr. Einstein. “We couldn’t do it without this expansion funding, and it means we can take it on with a team of individuals that includes trans people participating in an effective way.”