RESEARCH SUMMARIES 2017 - o - MS Society of Canada
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o RESEARCH SUMMARIES 2017
TABLE OF CONTENTS
Discovery and Innovation…………………………………………1
Cultivating the Next Generation of Top MS Researchers……2
endMS Training Programs………………………………………….3
Translational Programs……………………………………………..4
Wellness Programs……………………………………………...…..5
Research Review Process………...……………………………….6
Community Representatives………………...……………………7
Research We Fund………………………………………...………..8
Newly Funded Research Projects………………………...……...9
Mechanisms of Disease……………………...………………9
Symptom Management and Quality of Life…..……….13
Cause and Risk Factors………..…………………………..14
Therapy and Clinical Tool Development…..…………..15
New Master’s Studentships………..…………………………….16
New Doctoral Studentships ……………………..………...……16
New Postdoctoral Fellowships…………………..……………...17
Ongoing Research Projects………..……………………………18
Mechanisms of Disease………...………………………….18
Symptom Management and Quality of Life……..…….24
Cause and Risk Factors……………..……………………..25
Therapy and Clinical Tool Development..……………..29
Renewed Master’s Studentships……..…………………………34
Renewed Doctoral Studentships……….....……………………34
Renewed Postdoctoral Fellowships…………………………....35
Collaborative Grants…………………………………..…………36
DISCOVERY & INNOVATION
BREAKDOWN OF MS RESEARCH
The MS Society has funded research in multiple sclerosis since the first grant of $10,000
was awarded in 1949. It is now, along with its affiliated MS Scientific Research Foundation,
the single largest funder of MS research in Canada. Through the administration of operating
grants, studentship awards, postdoctoral fellowships, career development awards, targeted
research grants, and multi-site collaborative team grants, the MS Society and MS Scientific
Research Foundation are committed to advancing research that investigates all aspects of
multiple sclerosis, and fostering a strong network of talented researchers and trainees
across the country. Investing in this research network also leads to increased national and
international collaboration, facilitation of translation of new discoveries into treatments,
and ongoing scientific training.
$6M Committed in New Operating Grants and Personnel Awards
$11M Committed in Ongoing Operating Grants and Personnel Awards
14 New Operating Grants Awarded 47 Active Operating Grants
13 Funded Postdoctoral Fellows
23 Research Institutions hosting
22 Funded Doctoral Students MS Society funded investigators
9 Funded Masters Students
3 Ongoing Collaborative Team Grants $8.2M Ongoing Commitment
to Collaborative Team Grants
4 Ongoing Wellness Projects
4 New Translational Research Projects
1
CULTIVATING A NEW GENERATION
OF TOP MS RESEARCHERS
The MS Society invests in the next generation of MS research leaders by
supporting promising young investigators with a range of trainee awards and
through education and training programs.
OPERATING GRANTS
The operating grant program is intended to support the generation of new scientific
knowledge and applications that will improve health and quality of life of people affected
by MS. These investigator-initiated research proposals must demonstrate relevance to MS
and pertain to the biomedical or clinical and population health research streams.
endMS STUDENTSHIP AWARDS
These awards are a key plank of the MS Society’s research training program. They support
talented students enrolled in graduate school who are keen on developing their knowledge
and research skills in MS.
endMS POSTDOCTORAL FELLOWSHIPS
Following completion of their graduate studies, postdoctoral fellows are intent on building
their research career and applying what they have learned to solve complex research
questions. The MS Society’s postdoctoral fellowship awards help to retain promising
trainees in the MS field by providing them with support during an important time of growth
and transition.
endMS CONFERENCE
The largest MS-focused scientific conference in Canada, aimed at fostering knowledge
exchange on MS-related research, networking opportunities, and collaboration among
researchers and trainees. Last year, the endMS conference was held from December 6-9 in
Toronto, ON. The conference included four sessions focused on different themes (cognition
and behavior, neuroimmunology, repair and neuroprotection, and progressive MS), the
HEAR MS day which was dedicated to building and strengthening connections between
trainees and people affected by MS, as well as poster presentations which allowed
researchers to interact one-on-one with their scientific peers to share their study and
gather feedback on advancing their research. The next endMS Conference will be held in
2019.
2
endMS TRAINING PROGRAMS
endMS SPRINT
The endMS SPRINT (Scholar
Program for Researchers IN
8
Training) is a national training
program designed for trainees endMS SPRINT
at the Master’s, Doctoral, and
PARTICIPANTS IN 2017
Postdoctoral/Clinical Fellowship levels who are keen on
enhancing knowledge and skill in MS research, taking part
in interdisciplinary, collaborative research and establishing
valuable connections amongst peers in the field. Trainees
who are accepted in the SPRINT program participate in
two consecutive annual endMS Summer Schools including
career development sessions, as well as in active learning
58
components that are pursued throughout the academic
endMS SPRINT
year.
PARTICIPANTS SINCE
“The interdisciplinary projects
encourage trainees to explore MS- 2011
related topics outside of their own
field with an interdisciplinary group of
colleagues. This interaction fosters
the development of a variety of skills
that are crucial to conducting
meaningful research, and that can
often not be obtained in individual
academic programs.”-endMS
SPRINTer
40
endMS SUMMER SCHOOL
endMS SUMMER
The endMS Summer School is an annual interactive
SCHOOL PARTICIPANTS
education program that aims to enhance knowledge and
skills in MS research among trainees. Each year, Summer
IN 2017
School brings together trainees from a variety of
disciplines to learn about one central MS-related theme
and the focus alternates between basic one year and 333
clinical and population health research the next.
The theme of 2017 endMS Summer School was “Moving endMS SUMMER
MS research forward through clinical and biomedical
SCHOOL PARTICIPANTS
partnerships.”
SINCE 2009
3
CENTRE FOR DRUG
RESEARCH AND
DEVELOPMENT (CDRD)
The MS Society of Canada
TRANSLATIONAL PROGRAMS
continues to work with
Vancouver-based non-profit TRANSLATING MS RESEARCH DISCOVERIES
organization CDRD, which boasts
INTO NEW THERAPIES
an extensive drug development
and commercialization platform. Turning novel findings in the laboratory into life-saving
By supporting projects in outcomes for people living with MS as quickly as possible
conjunction with CDRD, the MS is a top priority for the MS Society. This can be achieved
Society is helping researchers by investing in translational research, which aims to test
translate their research findings
into tangible clinical outcomes.
and validate early stage discoveries in order to make
them viable for clinical trials.
Project highlight:
In 2017 the MS Society funded Dr.
Philippe Séguéla (McGill
University). In collaboration with
CDRD, Dr. Séguéla is screening
compounds that will prevent
cellular injury and CRITICAL GAP
neurodegeneration in progressive
MS. Clinical Approved
Basic
Development treatment for
Research
/ Trials MS
FAST FORWARD Translational
Research
Fast Forward is a non-profit
subsidiary of the US National
Multiple Sclerosis Society (NMSS)
that connects academic and
clinical researchers with private-
sector drug development in order
to develop and advance innovative
MS therapies.
The MS Society is a key player in a number of exciting
Project highlight: new initiatives that are designed to bridge this “critical
In 2017 the MS Society co-funded gap” between basic discovery and clinical research. Read
Dr. Fang Liu (Centre for Addiction the side bar to get a glimpse of how the MS Society is
and Mental Health), who is
optimizing a series of compounds
leveraging existing resources and expertise, and building
that contributes to nerve cell collaborative partnerships in translational research.
death. Having already funded her
earlier discovery work in the lab
that uncovered these unique drug
properties, the MS Society
continues to support Dr. Liu as she
attempts to transform these
molecules into effective drugs for
4
MS.
Hermès Canada | MS
WELLNESS PROGRAMS Society Wellness
Research Innovation
MS WELLNESS SURVEY IGNITES RESEARCH TO Grant
IMPROVE QUALITY OF LIFE Generous support from
Hermès Canada enabled
The MS Society reached out to people affected by MS
funding for three projects that
with the MS Wellness Survey. Respondents were asked are addressing key gaps in
which areas of wellness are most important to them in wellness that were highlighted
improving their quality of life. The survey received an in the MS Wellness Survey:
overwhelming response from the MS community, with • Dr. Charity Evans
1,032 people affected by MS from across Canada (University of
providing input. Saskatchewan) is testing
SURVEY RESULTS: the impact of a Pilates
program on MS.
NUTRITION: PHYSICAL ACTIVITY: • Dr. Katherine Knox
(University of
Saskatchewan) is
developing a web-based
physiotherapy program
for moderate to severe
MS.
• Dr. Ann Yeh (University of
Toronto) is developing a
mobile app to increase
activity levels in youth
with MS.
EMOTIONAL WELL-BEING: Hack4Health
Hack4Health is an annual,
health-based hackathon
hosted by the University
Waterloo. Teams of students
from all departments come up
The MS Society is funding research that will provide with creative solutions for
information on wellness approaches for people with MS, people living with degenerative
and that will ultimately improve their health and quality of neurological conditions.
life. By engaging members of the MS community,
Project highlight:
researchers will be better equipped to identify specific
questions that are relevant to the community, people In 2017 the MS Society funded
Team Roze who is working
affected by MS will be empowered to actively contribute to
with Dr. Karla Boluk to develop
research, and an immediate impact can be delivered to
a fitness app for women in MS.
people affected by MS in the clinic, at home, and in the
community. 5
Review Committees
Each research review committee
is tasked with carefully
RESEARCH REVIEW PROCESS
evaluating applications that fall
within their expertise. They The principal aim of the MS Society is to stimulate and support
include scientific reviewers, innovative research in multiple sclerosis. The Society is
members of the community, a
chair who presides over the
committed to ensuring that research of the highest quality and
review process, and a scientific scientific merit is funded. Each application submitted to any one
officer who takes detailed notes of the MS Society’s research funding opportunities is rigorously
and provides a summary of scrutinized by experts in the field and people affected by MS;
review comments to the
applicants. Below is a list of their role is to identify the proposal’s strengths and weaknesses,
current review committees for and determine whether the research will advance knowledge in
the MS Society: the field and/or improve health and quality of life. Check out our
• Biomedical Research Review review process below:
Committee: this committee
reviews operating grant
applications for research that Review Committees (September- January)
uncovers the biological,
pathological, and mechanistic Scientific Reviewers Committees Committees
aspects of MS, and provides experts and assigned review discuss and
community
fundamental knowledge applications by applications rank
members invited
MS Society (at home application
about the development and by MS Society to
based on area review)
form review (in-person
progression of disease. committees of expertise
review)
• Clinical and Population
Health Research Review
Committee: this committee Medical Advisory Committee (February)
oversees operating and pilot
grant applications for
Meritorious
research studies investigating applications MAC reviews
the epidemiology, health and makes a
recommended
final
economics, and risk factors for funding to
recommendatio
MAC
for MS. n to the Board
• endMS Personnel Awards
Review Committee: this
committee reviews
applications for Master’s and MS Society Board of Directors
Doctoral Studentship awards
as well as Postdoctoral
Fellowships in both Issues final
Board reviews and approval for
biomedical and discusses
funding
clinical/population health recommendations
research.
6
COMMUNITY REPRESENTATIVES
In 2012, an initiative was launched to involve people in the MS What Community
community – termed Community Representatives – in the Representatives Review?
research review process. Community Representatives are people
who have a personal connection to MS, and thus are able to Community representatives
comment on how the research will influence their day to day living review parts of a grant and
and what the outcomes of the research mean to them and the award application that are
broader MS community. Through the engagement of Community prepared for a lay audience,
Representatives in the review process, the MS Society aims to specifically the lay summary,
provide a venue for people affected by MS to have their voices relevance to MS, and training
heard in regards to research, while at the same time having the background sections. They
opportunity to learn more about the ongoing research that is provide an enthusiasm rating
happening in Canada. and comment on the following:
2017 Community Representatives:
• Comprehension/accessibilit
y of the lay summary,
relevance and training
sections
• Relevance of the research
Shannon Bachorick Coriann Berry Jennifer Charters to critical needs and
challenges faced by people
affected by MS
• Capacity for the project to
yield outcomes that will
improve the health and of
quality of life of people for
Sarah Flohr Lynda Gregson Kim McIntyre people affected by MS.
Derek Milloy Corrie Shaw Kristen Robillard
7
RESEARCH WE FUND IN OPERATING GRANTS
THERAPY AND CLINICAL CAUSE & RISK FACTORS
TOOL DEVELOPMENT
Studies in this area help identify and test new Despite decades of research, the cause of MS
biological targets and diagnostic methods, is still a mystery. Researchers are pointing to a
which can lead to the development of viable combination of biological, environmental and
therapies for people living with MS. This lifestyle triggers that contribute to risk for MS.
research focuses on areas such as clinical Knowing what these triggers are and how they
trials, drug repurposing, imaging, and health- influence one another is a critical step towards
based technological applications. understanding and developing a cure for this
perplexing and often unpredictable disease.
MECHANISMS OF DISEASE SYMPTOM MANAGEMENT &
QUALITY OF LIFE
The initiation, progression, and dissemination MS is a chronic condition that can have
of MS are important areas of focus for studies enormous impacts on a person’s ability to
in this category. Researchers are exploring carry out everyday tasks, stay active, engage
the structural and functional changes that in social relationships and live life to its fullest
occur in MS, including inflammation, potential. Studies in this area are focused on
neurodegeneration, and myelin repair. improving our understanding of how MS
affects daily living and identifying ways to
overcomer barriers and effectively manage
symptoms.
8NEWLY FUNDED PROJECTS (2017)
MECHANISMS OF DISEASE
Dr. Nathalie Arbour
Centre de Recherche du CHUM
Funding: $383,138.25
Term: April 1, 2017 – March 31, 2020
Impact of IL-27 on MS pathobiology
The role of the immune system is to protect us from invading microbes, but in MS,
malfunctions in the system cause inflammation and attacks on parts of the brain as if they
were foreign invaders. Dr. Nathalie Arbour’s research aims to identify molecules present in
the brains of people living with MS that are used by the immune system to attack it. Her
research is specifically looking at a molecule called IL-27, which has previously shown to
block inflammation. She wants to examine if the quantity of IL-27 present in individuals with
MS is a good indicator of the disease activity as well as the type of MS. So far, she has shown
evidence that IL-27 triggers different responses in white blood cells from people with MS
compared to those from healthy individuals. Dr. Arbour’s research project will also dissect
the effects of IL-27 on astrocytes, which are called the “house-keeping” cells of the brain.
This research potentially offers a new target in the pathophysiology of MS as well as may led
to development of novel biomarkers in the disease.
Dr. Soheila Karimi
University of Manitoba
Funding: $358,321.00
Term: April 1, 2017 – March 31, 2020
Role and therapeutic potential of Neuregulin-1 as a modulator
of neuroinflammation and remyelination in multiple sclerosis
Loss of or damage to myelin, the protective covering over nerve fibers, is one of the more
well-known characteristics of MS. Dr. Karimi’s research team has identified a protein called
Neuregulin-1 which is important for the development of oligodendrocytes, the myelin-
producing cells. Neuregulin-1 is significantly reduced in MS lesions and can be a cause for
failure in myelin repair. Increasing Neuregulin-1 is theorised to enhance oligodendrocyte
replacement, protect nerve fibers, and reduce scar formation. Dr. Karimi’s project will
determine the role of Neuregulin-1 in demyelination and neurodegeneration using animals
that have an MS-like disease. To perform this research, both genetic and pharmacological
approaches will be used to reduce or enhance the activity of neuregulin-1. As many of the
current MS therapies work by suppressing the immune response, there is a need to identify
effective therapies that specifically repair and renew damaged myelin. Dr. Karimi’s research
team hopes to identify neuregulin-1 as a potential target of the repair process of myelin.
9Dr. Timothy Kennedy
Montreal Neurological Institute, McGill University
Funding: $360,300.00
Term: April 1, 2017 – March 31, 2020
Identifying New Molecular Mechanisms that Promote
Myelin Maintenance and Remyelination
Myelin is the protective covering produced by cells called oligodendrocytes which surround
nerve fibers. Dr. Kennedy studies the pathways of repair in the brain, in particular the
connections between oligodendrocytes and nerve fibers. He has previously found that a
protein called netrin-1 plays an important role in myelin production and repair processes. His
group is working to understand how netrin-1 contributes to the initial formation and
maintenance of myelin during development, and in the adult brain, and how targeting the
function of these proteins may promote remyelination. MS is a result of both damage to
myelin as well as a poor repair response. By figuring out the repair process down to the very
last detail, in particular the role netrin-1 plays, Dr. Kennedy and his team may enable the
development of treatments that enhance repair in people with MS, which is a vital step in
preventing further damage, slowing disease progression and allowing people to regain
neurological function.
Dr. Bradley Kerr
University of Alberta
Funding: $342,494.00
Term: April 1, 2017 – March 31, 2020
Examining sex differences in neuropathic pain behaviours
in the EAE model
Pain is a major component of MS; it is estimated that over 50% of people living with MS
experience chronic, neuropathic pain. Dr. Bradley Kerr’s previous MS Society-funded research
determined differences in pain between sexes in mice with MS-like disease. His research
team also reported that differences in pain sensitivity can be impacted by daily exercise.
Using the results of his previously funded research project, Dr. Kerr plans to explore if pain
sensitivity can be modulated with an anti-inflammatory treatment of MS and if different
responses are seen in male and female mice with MS-like disease. Furthermore, Dr. Kerr
research plans to explore if oxidative stress, a process that causes neurodegeneration in MS,
is altered between different sexes and hence is contributing to different pain sensitivities in
MS. His goal is to generate important insights into the mechanisms underlying pain in MS,
which will pave the way for more effective therapies.
10Dr. Rashmi Kothary
Ottawa Hospital Research Institute
Funding: $301, 920.00
Term: April 1, 2017 – March 31, 2020
MicroRNA-145 is a key regulator of oligodendrocytes
maturation and CNS myelination
Dr. Rashmi Kothary’s research team is looking deep into the genetic code of oligodendrocytes
– the myelin-producing cells in the brain - to see if there are any important clues that will
reveal why myelin repair is inefficient or blocked in people with MS. His findings to date
revealed an increase in expression of a genetic molecule, MiR-145, in MS lesions. His
research’s team plans to test if increasing and decreasing the quantity of MiR-145 in both a
cellular and animal model of MS-like disease will be beneficial or detrimental in the
progression of MS. Dr. Kothary hopes that the findings from these studies will have an impact
on the development of future therapeutic strategies targeting myelin repair, which is crucial
in MS.
Dr. Shalina Ousman
University of Calgary
Funding: $314,776.62
Term: April 1, 2017 – March 31, 2020
Elucidating the role and regulation of
astrocytes in multiple sclerosis.
A protein known as Cystatin C is elevated in people with MS but its function remains unknown.
Dr. Shalina Ousman and her research team discovered that Cystatin C is also increased and
plays a detrimental role in mouse models of MS-like disease and is expressed in the house-
keeping cells of the brain called astrocytes. Dr. Ousman’s current research aims to determine
if Cystatin C has a detrimental role through its regulation of astrocytes and if this in turn is
altering the immune response seen in MS. This work will provide a better understanding of
the pathophysiology of the MS disease and could lead to a new therapeutic target in MS.
11Dr. Manu Rangachari
Université Lavel
Funding: $299,259.00
Term: April 1, 2017 – March 31, 2020
Investigating a novel inhibitory signaling mechanism that
represses T cell-driven CNS autoimmunity
Loss of myelin contributes to MS disease. Dr. Rangachari’s goal is to identify genes that can
lessen the immune cell’s attack on myelin. His research team has already found a specific
gene called Serpine1 reduces damage to the myelin caused by the harmful T cells from the
immune system in an animal that mimics MS disease. The goal of the current research
project is to further delineate how Serpine1 works in MS. As MS is a disease caused by both
the immune and nervous systems, the research team will also determine which system
Serpine exhibiting its benefit on. A current approved MS drug called fingolimod (Gilenya) is
suggested to turn on the expression of Serpine1 and this might explain how fingolimod
improves MS. Dr. Rangachari’s research team plans to understand this process further.
Dr. George Robertson
Dalhousie University
Funding: $300,185.00
Term: April 1, 2017 – March 31, 2020
Gait parameters as predictors of functional recovery
in a mouse model of MS
At least nine different types of drugs have been shown to stimulate remyelination and reduce
motor deficits in mice. Dr. Robertson’s aims to determine which of the nine drugs are most
likely to improve mobility of MS patients by stimulating myelin repair. To evaluate this, the
research team will use a method called kinematic gait analyses. Gait analysis observes the
complex joint movements of a leg that occur during walking into specific parts. For example,
improved ankle movement during walking is closely linked with increased myelin repair. This
technique will be used to determine which of the 9 drugs best improves the leg movements in
animal models of MS. Dr. Robertson hopes to establish a sensitive analytic tool of movement
analysis for selecting the most promising therapeutic compounds for human testing that will
improve the mobility in individuals with MS.
12Dr. Alain Simard
Université de Moncton
Funding: $355,821.00
Term: April 1, 2017 – June 30, 2020
Characterizing the anti-inflammatory and disease-modifying
potential of novel a7 nicotinic acetylcholine receptor silent agonist
Nicotine has been shown to be protective against disease in mice that have MS-like symptoms.
The beneficial effect of pure nicotine is not to be confused with smoking, which aggravates
MS due to many other chemicals found in cigarette smoke. Dr. Simard’s project plans to test
new molecules that were recently created to recapitulate nicotine’s effect on immune cells,
thereby avoiding the side effects of less specific compounds. These molecules have very
potent anti-inflammatory properties and may be promising disease-modifying drug
candidates. The objective of the project is to understand if these novel molecules inhibit
inflammation, and whether these insights can be applied to all forms of MS.
SYMPTOM MANAGEMENT AND QUALTIY OF LIFE
Dr. Marcia Finlayson
Queen’s University
Funding: $268,789.83
Term: April 1, 2017 – March 31, 2020
A multi-site randomized controlled trial of MS INFoRM: An
interactive fatigue management resource for persons with MS
Nearly two-thirds of people with MS experience fatigue, which can negatively impact
employment, quality of life, and ability to engage in a full range of daily activities. To target
this platform, Dr. Finlayson’s group developed MS INFoRM (Multiple Sclerosis: An Interactive
Fatigue Management Resource), a self-directed resource that addresses key components of
managing MS fatigue in the context of daily life. Her study will determine whether MS INFoRM
contributes to reducing fatigue. They will also look at whether it improves other important
outcomes like cognition, feelings of self-worth, depression, and participation and
independence. The goal of this study is to improve access to fatigue management in Canada
and beyond.
13CAUSE AND RISK FACTORS
Dr. Marc Horwitz
University of British Columbia
Funding: $354,048.00
Term: April 1, 2017 – March 31, 2020
Elucidating the mechanistic role of latent EBV
infection in the etiology of MS
Epstein-Barr virus (EBV), best known as the cause of infectious mononucleosis (mono), is
believed to play a role in the cause of MS. The risk of developing MS is 10 times greater in
individuals infected with EBV during childhood, and 20 times greater in those who have
developed mononucleosis. In his previous grant funded by the MS Society, Dr. Horwitz
identified that mice infected with an EBV-like virus developed a disease highly reminiscent of
MS. His current project builds on these findings to further examine the mechanism by which
EBV influences the development of MS. The ultimate goal of Dr. Horwitz’s project is to refine
therapeutics to interrupt these specific EBV-immune interactions and prevent MS.
Dr. Dalia Rotstein
University of Toronto
Funding: $156,040.00
Term: April 1, 2017 – March 31, 2019
Immigration and the risk of multiple sclerosis
Studying rates of MS amongst immigrants to Canada can help to understand why Canada is one
of the highest risk regions for MS in the world. Immigrants are thought to be at lower risk for
developing MS than people born in Canada, but their risk is still believed to be higher than
that in their native countries. In this study, Dr. Rotstein’s work, which will study the risk of
developing MS amongst immigrants in Ontario, may lead to the creation of the largest and
most diverse cohort of immigrants with MS. Administrative data will be used to understand
how access to health resources for immigrants with MS compares to access for Canadian-born
individuals with MS. These findings will allow health professionals to tailor their care to the
unique needs of the immigrant population with MS, while also providing important insights
into risk factors for MS in general.
14THERAPY AND CLINICAL TOOL DEVELOPMENT
Dr. Shannon Kolind
University of British Columbia
Funding: $292, 500.00
Term: April 1, 2017 – June 30, 2020
Establishing an imaging biomarker for
disease progression in multiple sclerosis
Biomarkers are biological clues from the body that can tell us about the state of a disease or
the effect of a treatment. The most promising brain imaging biomarker in MS is change in
brain volume, however this can take over a year to confirm and is only partially linked to
progression. As a potential alternative, Dr. Kolind’s research team wants to explore the loss
of myelin as a potential biomarker. The integrity of myelin determines the health of neurons,
and myelin loss can reflect the severity of MS disease. Dr. Kolind’s research team plans to use
imaging tools that can detect and measure structural changes in myelin, which in turn can
provide information about disease progression. Dr. Kolind hopes that her findings will help
to: (1) establish an approach that monitors myelin changes; (2) identify individuals at risk for
severe progression; and (3) reduce the cost and time required for progressive MS clinical
trials.
Dr. Alan Wilman
University of Alberta
Funding: $280,500.00
Term: April 1, 2017 – June 30, 2020
MRI of Deep Grey Matter in multiple sclerosis
Magnetic Resonance Imaging – or MRI – is a powerful tool that enables clinicians and
researchers to diagnose and monitor MS, as well as assess the effects of treatments. Research
in this field is advancing quickly, however appropriate imaging measures that accurately track
disease progression remain elusive. Dr. Alan Wilman’s project plans to test new MRI methods
that may enable better tracking of MS by examining the whole brain. The idea is to create
new ways of performing MRI that are specific to particular biological changes that occur in
the brain (not just in lesions) such as examining deep parts of the brain that are linked to
movement and where iron is stored in the brain. This work will advance the understanding of
MS by examining the brain with new MRI methods that reveal different processes that are
currently not tested in the clinic with the hope to enable physicians to make a more effective
assessment of MS disease state and understand the effects of therapy.
15Master’s Studentships (Newly Funded in 2017)
Name Institution Project Title
Leina Saito University of Alberta Innate Immune Responses in
Oligodendrocytes and Therapeutic
Strategies.
Yang Zhang Montreal Neurological Neuroprotective effects and mechanisms
Institute, McGill University of miR-223 in neurons in multiple
sclerosis
Carina Graf The University of British Magnetic Resonance Imaging and
Columbia Histology of post-mortem Spinal Cord in
Multiple Sclerosis
Diana Valdés Cabrera University of Alberta High Resolution Diffusion Tensor Imaging
and Fiber Tractography in White Matter:
An Approach to Studying the Relationship
of Microstructural Changes to Disability in
Multiple Sclerosis
Ana Catuneanu University of Alberta Examining sex differences in central
nervous system plasticity and pain in a
mouse model of Multiple Sclerosis
Ellinore Doroshenko University of Toronto Sex Differences in T helper cell expansion
as a cause of sex differences in EAE
Doctoral Studentships (Newly Funded in 2017)
Name Institution Project Title
Marc Charabati Centre de Recherche du Centre MCAM+ Cells Contribute to the
Hospitalier de l’Université de Development of MS and Predict its
Montréal Progression
Jessica Allanach The University of British A humanized mouse model of MS to study
Columbia EBV infection in disease
Kevin Thorburn University of Alberta Development and characterization of
animal models to study MS-related
trigeminal neuralgia
Marjan Gharagozloo Université de Sherbrooke NLRX1 acts as an endogenous inhibitor of
multiple sclerosis
Samantha Kornfeld Ottawa Hospital Research Uncovering and reversing causes of
Institute remyelination failure in progressive
multiple sclerosis - miR-145-5p regulates
MYRF in oligodendrocytes
16Dylan Galloway Memorial University Exploring the Clinical and Functional
Significance of Altered MiR-223
Expression in Multiple Sclerosis and its
Animal Models
Jesse Huang Karolinska Institutet Host genetic influence on humoral
immunity to viral infections and its role
in multiple sclerosis and progressive
multifocal leukoencephalopathy
Hanwen Liu The University of British Diffusely Abnormal White Matter in
Columbia Different MS Phenotypes: Impact on
Myelin, Axons and Brain Volume
Postdoctoral Fellowships (Newly Funded in 2017)
Name Institution Project Title
Kate Parham Western University Advanced in vivo imaging of disease
causing T and B cells in a model of anti-
myelin autoimmunity
Evelyn Peelen Centre hospitalier de The effect of the Th17-associated
l'université de Montréal cytokine IL-26 on CNS barriers integrity:
Implications for MS
Peggy Assinck University of Edinburgh Innate and Adaptive Remyelination
Zohreh (Solmaz) The University of British Human immunodeficiency virus,
Setayeshgar Columbia antiretroviral drugs and multiple sclerosis
risk (HIV-MS)
Katharine Harding The University of British Is socio-economic status associated with
Columbia disability progression in MS? A multi-
national study
Corey Arnold University of Calgary A novel mechanism of autoinflammatory
induction by cysteine protease Cathepsin
Z in multiple sclerosis
Asanga Weliwitigoda Benaroya Research Institute at Establishing the role of DOCK8 in T and B
Virginia Mason cells in a murine model of MS
Barbara Morquette Montreal Neurological Immune cells influence on
Institute, McGill University neurodegeneration and neuroprotection
through neuronal microRNAs regulation in
the optic nerve
17ONGOING PROJECTS (FUNDED PRIOR TO
2017)
MECHANISMS OF DISEASE
Dr. Samuel David
McGill University
Funding: $376,492.00
Term: April 1, 2014 – March 31, 2017
Role of M2 macrophage subtypes and iron in Experimental
Autoimmune Encephalomyelitis
Although inflammation is generally regarded to be a harmful process in the MS brain, certain
types of immune cells have been found to have beneficial effects on the disease. Dr. Samuel
David is examining a type of anti-inflammatory immune cell called M2 macrophages which
reside in MS lesions. The goal of Dr. David’s study is to determine if transplanting M2
macrophages into mice with an MS-like disease can improve their symptoms. Since beginning
the project, Dr. David has surprisingly found that transplanting control macrophages called M0
was more effective in reducing paralysis in mice with MS-like disease compared to M2
macrophages. Ongoing work will involve exploring whether increasing the number of
macrophages along with molecules that facilitate communication between immune cells will
reduce disability in animals with MS-like disease.
Dr. Jennifer Gommerman, Ph.D.
University of Toronto
Funding: $ 365,500.00
Term: April 1, 2016- March 31, 2019
Immune cell-microbiome interactions and neuroinflammation
The immune system has the ability to "put the brakes" on inflammatory responses when
required. In MS, for reasons that are not understood, this breaking mechanism is impaired.
The proposed research from Dr. Gommerman’s group seeks to broaden understanding of
immune regulation by focusing on a specific immune cell called B cells. Preliminary data
suggests that some B cells have an anti-inflammatory function, and that B cells in general are
influenced by microbes that live in the intestines (gut microbiome). The aims of the proposed
research are to determine how gut microbes influence MS in mice, determine how the
microbiome influences B cell function in mice with MS-like disease, and determine how
microbes in the gut influence the brain and spinal cord. The team has already discovered that
the gut microbes have a role in dictating disease severity in mice with MS-like disease that
have compromised B cell function. Surprisingly, they also discovered that this is particularly
true of male mice. This research will delineate how B cells function in MS to establish better
drugs that target B cells to treat MS.
18Dr. Craig Moore, Ph.D.
Memorial University of Newfoundland
Funding: $ 344,104.00
Term: April 1, 2016- March 31, 2019
Impact of MicroRNA-223 on Immune and Glial Cells in Multiple
Sclerosis
Dr. Craig Moore and his team are studying specific molecules called microRNAs, which are
potential new targets for progressive MS treatment. Found in both brain and immune cells,
microRNAs play an important role in controlling inflammation and tissue repair in the
damaged brain. The Moore lab discovered one microRNA molecule in particular-called mir-
223- to be important in promoting repair in MS. To characterize the role of mir-223 in detail,
the Moore lab is growing cells in a dish and treating them with mir-223 to determine the
change in the levels of inflammatory signals. Future work from this lab aims to investigate the
role of mir-223 in animal models of MS. Dr. Moore hopes that this research will identify a
novel target that could be further explored for treating both relapsing and progressive forms
of MS.
Dr. Catherine Pallen
The University of British Columbia
Funding: $300,000.00
Term: April 1, 2015 – March 31, 2018
Role of PTP Alpha in oligodendrocyte maturation and
myelination/re-myelination
Dr. Catherine Pallen’s laboratory has spent many years studying a small molecule called
protein tyrosine phosphatase alpha (PTPa). Their findings, and that of others, have shed light
on the molecule’s importance to the development of oligodendrocytes (myelin-producing cells
in the central nervous system). Now, the team is set to explore how interactions between
PTPa and other neighbouring molecules can, together, guide oligodendrocytes to grow and
produce myelin in cell culture. They will also seek to understand the possible role PTPa plays
in the regeneration of destroyed myelin. Thus far, Dr. Pallen’s research team has discovered
that PTPa promotes the development of oligodendrocytes, mediates interactions between
neurons and oligodendrocytes, and promotes the myelination of nerve fibers. Ongoing work is
exploring the mechanisms through which PTPa exhibits its effects on neurons and
oligodendrocytes. Together these findings provide a foundation for the development of
therapies that promote myelin repair and reverse or ameliorate the debilitating effects of
demyelination in MS.
19Dr. David Picketts
Ottawa Hospital Research Institute
Funding: $306,960.00
Term: April 1, 2015 – March 31, 2018
Defining the requirements and therapeutic potential of VGF
in CNS remyelination
We know that exercise can alleviate many symptoms associated with MS, and in some cases,
slow disease progression. Precisely why is somewhat of a mystery. Previous research led by
Dr. David Picketts identified one possibility – a small molecule called VGF. Produced during
exercise, VGF supports the growth of myelin-producing cells, making it an excellent target for
treatment. Using various cell culture techniques, Dr. Picketts and his team will explore how
VGF stimulates myelination, test the efficacy of specific drugs to boost VGF production and
myelination, and investigate whether VGF can enhance remyelination in a pre-clinical MS
model. They will also assess whether exercise mimetics – drugs that can mimic or amplify the
effects of exercise – can improve remyelination, thus serving as a possible therapeutic
strategy for when physical exercise becomes too challenging. His team is currently trying to
understand if the removal of VGF is detrimental to the myelination process and if VGF is a
potential target for therapeutics to treat MS.
Dr. Christopher Power
University of Alberta
Funding: $400,517.89
Term: April 1, 2015 – June 30, 2018
CNS inflammasomes: defenders and disease
determinants in progressive multiple sclerosis
The human brain is home to structures called inflammasomes. These structures are made-up
of many different proteins that, when bundled together, activate the brain’s immune
response. Preliminary work from Dr. Christopher Power’s laboratory suggests that
inflammasomes may fuel the autoimmune attack in primary progressive MS. To test this
theory, Dr. Power and his team will investigate how inflammasomes affect brain anatomy and
function in primary progressive MS, as well as explore what molecules are responsible for
inflammasome activation in cultured human brain cells. The team will also test how
suppressing inflammasome activation affects mice with an MS-like disorder. The research
team has discovered an important inflammasome called NLRP3, which serves a central role in
the inflammatory response and activates cell death cascades, as well as other molecules that
regulate inflammasomes. Their findings will shed light on the role of the immune system in
primary progressive MS and potentially lay the groundwork for the development of biomarkers
and treatments for MS.
20Dr. Alexandre Prat
Centre de Recherche du Centre Hospitalier de l’Université
de Montréal
Funding: $404,688.00
Term: April 1, 2015 – March 31, 2018
DICAM: a novel molecular effector in neuroinflammation
Normally, the brain is not easily accessible to cells of the immune system, as it is surrounded
by a relatively impenetrable wall of cells called the blood-brain barrier. However, in MS, a
large number of immune cells are able to cross this barrier, leading to the formation of brain
lesions. Dr. Alexandre Prat and his team previously identified a possible tool that is used by
aggressive immune cells to by-pass the barrier: a molecule called DICAM. Using a combination
of experimental techniques, including analysis of cells from people with MS, Dr. Prat’s team
will explore which cells of the immune system express DICAM, and how these cells use DICAM
to cross the blood-brain barrier. The team will also test whether there is any benefit to
manipulating DICAM in mice with an MS-like disorder. The researchers’ overarching goal is the
eventual development of DICAM-targeting drugs that limit lesion formation in MS. Thus far,
the research team has demonstrated increased quantities of DICAM in people with relapsing-
remitting MS, compared to healthy donors. Furthermore, the data reveals that DICAM is
expressed on a type of white blood cells called T helper 17 cells (Th17), which are the leading
agents of inflammation in the central nervous system. Fortunately, Dr. Prat is investigating a
promising molecule called 9E9 which appears to block the migration of Th17 cells
subsequently reduce disability in animal model of MS-like disease.
Dr. Alexandre Prat
Centre de Recherche du Centre Hospitalier de l’Université de Montréal
Funding: $426,000.00
Term: April 1, 2015 – March 31, 2018
Role of Astrocytes and Endothelium in BBB regulation and CNS
Immunity
A layer of cells called the blood-brain barrier surrounds and protects the brain. Unfortunately
in MS, aggressive immune cells penetrate the barrier and cause damage and lesion formation.
Molecules made by either the blood-brain barrier itself, or supporting cells in close proximity
to the barrier help determine the barrier’s effectiveness at blocking unwanted immune
incursions. Using advanced cell culture techniques and genetically modified mice, Dr.
Alexander Prat’s laboratory will explore how three molecules produced by the blood-brain
barrier and supporting cells called astrocytes, help form a tight and impermeable blood brain
barrier. Thus far, Dr. Prat’s research team has discovered that therapeutically blocking one of
those proteins (netrin-1) reduces penetration of aggressive immune cells and leads to
decreased disability in animals with an MS-like disease.
21Dr. Stéphane Richard
Lady Davis Institute – Jewish General Hospital
Funding: $223,356.00
Term: April 1, 2015 – March 31, 2018
The role of the quaking proteins in oligodendrocyte
physiology and myelination
Within the oligodendrocyte, the brain’s myelin-producing cell, a vast array of proteins are
tirelessly at work; first, pushing the oligodendrocyte to generate myelin and then protecting
and sustaining the oligodendrocyte and myelin over a person’s lifetime. Using genetically
modified mice, Dr. Stéphane Richard and his team will study one of these proteins – Quaking 1
(QK1) – to determine how it supports and maintains oligodendrocytes and myelin at the
molecular and cellular levels; both during early development and then later in adult life.
They will also test whether QKI is necessary for remyelination, the ability of oligodendrocytes
to generate new myelin following injury to the brain and spinal cord. The research team has
already created genetically modified mice that lack the QK1 protein, and discovered that
these mice display characteristics suggesting that the protein may be important for
myelination and could be an important area to further study in the context of MS.
Dr. Wolfram Tetzlaff, Ph.D.
The University of British Columbia
Funding: $ 341,411.00
Term: April 1, 2016- March 31, 2019
Targeting Oligodendrocyte Maturation for the Study of Axonal
Survival
Myelin loss often leads to damage to nerve fibers, rendering them unable to communicate
with one another and causing them to die (degenerate). This loss of nerve fibers is thought to
underlie the progressive stage of MS. Previous research has identified a key molecule involved
in this process of remyelination during development is MYRF. Using genetically engineered
mice lacking MYRF, Dr. Tetzlaff’s research team has discovered that MYRF is required to
promoate remyelination. Furthermore, the team has removed MYRF from remylinating cells to
show inhibition of the remyelinaton process. The Tetzlaff research team now hopes to use
this established model system that prevents remyelination with the removal of MYRF to test
which drugs will preserve the demyelination of neurons.
22Dr. Valerie Verge
University of Saskatchewan
Funding: $297,783.00
Term: April 1, 2015 – March 31, 2018
Novel strategies to enhance intrinsic repair following
demyelination
By briefly reducing the amount of oxygen available for breathing and/or using short bursts of
electrical stimulation, Dr. Valerie Verge’s laboratory has managed to improve the nervous
system’s self-repair mechanism in rats. In her latest project, Dr. Verge’s research team will
test whether these two techniques can boost the spinal cord’s ability to repair nerve and
myelin damage in mice. Similar experiments to improve regeneration will be carried out in
mice with an MS-like disease. To date, the research team has completed studies showing that
brief electrical stimulation of demyelinating neurons changes the role of harmful immune
cells called macrophages from a pro-inflammatory response to a pro-repair response. Dr.
Verge is hopeful that the stimulating treatments will enhance remyelination, while also
protecting vulnerable and damaged axons – a goal of great importance for those living with
MS.
Dr. Robin Yates, Ph.D.
University of Calgary
Funding: $ 346,506.00
Term: April 1, 2016- March 31, 2019
Targeting novel functions of cysteine cathepsins to limit
neuroinflammation
Inflammation in MS is caused by cells of the immune system travelling to the brain and
releasing molecules called cytokines. These cytokines are used by immune cells as a way to
communicate with each other, and in MS they can prompt immune cells to cause damage to
the central nervous system. One important cytokine in MS is IL-1. The Yates research group
has evidence to suggest that a protein called cathepsin stimulates the release of IL-1 and that
mice that don’t have this protein show lower levels of brain inflammation and a milder MS-
like disease course. Dr. Yates’ research will break down role and mechanism of action of
cathepsins in MS. In the past year, the research team has identified the involvement of a
particular cathepsin in triggering IL-1 activation. This discovery will pave the way for further
understanding of the development of MS and will help explain why some courses of MS are
different than others.
23Dr. Wee Yong, Ph.D.
University of Calgary
Funding: $ 412,636.00
Term: April 1, 2016- March 31, 2019
Mechanisms and parameters of exercise-induced
remyelination in mice
Loss of myelin, the protective covering of nerve fibers, is a hallmark of MS. The Yong lab has
been researching various means to promote remyelination using mice with experimentally-
induced injury to the spinal cord. Given that physical activity is known to improve wellness in
people with MS, Dr. Wee Yong and his team are exploring whether physical exercise can
promote remyelination. They have generated exciting data demonstrating that mice who are
given free access to a running wheel following injury in the spinal cord form new
oligodendrocytes and myelin over two weeks compared to mice with injury that do not
participate in physical activity. The current grant proposal seeks to understand how physical
exercise promotes myelin repair, and determine the type, duration and intensity of physical
exercise that is needed for successful repair following neurological damage.
SYMPTOM MANAGEMENT AND QUALTIY OF LIFE
Dr. Audrey Hicks
McMaster University
Funding: $301,482.00
Term: April 1, 2014 – March 31, 2018
A community-based randomized controlled trial testing
implementation of the new Canadian Physical Activity
Guidelines for Adults with Multiple Sclerosis
Physical activity has gained a great deal of attention recently for its potential to help people
with MS manage their symptoms. Recently, new physical activity guidelines (PAGs) for people
with MS were released. The next step is to determine how best to implement these guidelines
in the broader community. Dr. Audrey Hicks is leading a controlled clinical trial with 3 aims:
to compare how individuals with MS follow the PAGs; to ensure that following the PAGs will
result in improved fitness, function and perceived quality of life; and to explore whether
following the PAGs will impact key risk factors for other conditions such as heart disease,
diabetes and stroke. Dr. Hicks has completed testing on 69 participants to date, and
discovered that participants that adhered to PAGs 75% of the time (during the 16 week study
period) experienced significantly improved strength, reduced fatigue, and improved mental
and physical health-related quality of life.
24Dr. Daria Trojan
McGill University
Funding: $284,712.15
Term: April 1, 2012 – March 31, 2018
A Randomized, Controlled, Clinical Trial of Continuous
Positive Airway Pressure Treatment of Obstructive Sleep
Apnea-Hypopnea in Multiple Sclerosis
Obstructive sleep apnea-hypopnea (OSAH) is the most common sleep abnormality in people
with multiple sclerosis (MS), and is associated with increased fatigue and pain. Dr. Trojan’s
preliminary research showed that treatment of sleep disorders (mostly OSAH) can markedly
improve fatigue and other symptoms in some MS patients. The goal of this project is to test
the effect of OSAH treatment in a scientifically rigorous study to confirm improvements in
sleep quality, fatigue and other symptoms that dictate the quality of life in MS. The best
treatment for OSAH in the general population is continuous positive airway pressure (CPAP).
Thus far, Dr. Trojan has confirmed the observation of OSAH in individuals with MS and tested
the feasibility of the research to support long-term CPAP treatment. Over 40 individuals with
MS have been recruited to participate in the study with nearly 25 that have already
completed the trial.
CAUSE AND RISK FACTORS
Dr. Karen Davis
Krembil Research Institute
Funding: $200,767.00
Term: April 1, 2015 – March 31, 2018
The pain connectome in Multiple Sclerosis
Over half of all people living with MS experience chronic pain. Why some individuals
experience pain and others do not remain a mystery. A possible answer lies in the strength
and dynamics of the brain’s pain network – a series of interconnected brain areas that
collectively dictates a person’s pain experience. Using advanced magnetic resonance imaging
(MRI) techniques, Dr. Karen Davis and her team will explore the relationship between the
health and activity of connections within this network and MS-related pain. The research will
provide much needed insight into why and how the brain misinterprets or creates pain signals
in MS. This holds the promise of creating individualized, targeted therapeutics to modify or
alter a maladjusted pain network. Thus far, the research team has recruited and tested 40
healthy participants on behavioural tests and acquired brain imaging data. Furthermore, Dr.
Davis has established a collaboration with the MS Clinic at the St. Michael’s Hospital and have
initiated recruitment of patients at that site as well.
25Dr. Shannon Dunn, Ph.D.
Toronto General Research Institute
Funding: $346,896.00
Term: April 1, 2016- March 31, 2019
Sex and Central Nervous System Autoimmunity
MS affects three times more women than men. The reasons for this sex difference in MS
incidence are still unknown. Some studies have provided evidence showing that the immune
response is more vigorous in women than men, which would explain why an autoimmune
attack on myelin is more likely to happen in women. Dr. Dunn’s research team plans to
explore this idea further. Her lab has already revealed that an inflammatory factor called IFN-
γ is released in female, but not male rodents. The team will attempt to expand on this
finding to people with MS and determine if women have more active immune systems that
attack myelin than those in males.
Dr. Anthony Feinstein
Sunnybrook Research Institute
Funding: $282,227.80
Term: October 1, 2015 – September 30, 2018
Coming off cannabis in MS: a longitudinal, cognitive
and fMRI study
Between 40% and 60% of people living with MS experience difficulties with their cognitive
functioning. Cognitive impairment is associated with greater difficulty in securing a job,
functioning socially and pursuing leisure activities. Almost one in five people with MS report
using cannabis (marijuana) for symptom relief, most notably for pain and spasticity. However,
new evidence indicates that smoking cannabis may worsen cognitive function in MS. What is
not known, however, is whether these cognitive changes are reversible if a person with MS
stops smoking cannabis. Dr. Feinstein and his team will pursue this question by performing
cognitive testing and brain imaging on two groups of participants: one group will be
instructed to stop using cannabis while the other will be allowed to continue, and both groups
will be followed for 28 days. Preliminary data suggests that individuals with MS who abstain
from cannabis use show less cognitive impairment. Overall, the results of this project will be
important in educating people living with MS and physicians alike about the effects of
cannabis on cognition.
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