Thanks to generous, forward-thinking donors, MDC funds high-quality research across all neuromuscular disorders, that can advance knowledge and practice in the following areas and ultimately lead to cures for neuromuscular disorders:

  • causes of disorders and progression;
  • discovery of novel treatments, therapies and cures;
  • enhancement of clinical care;
  • and, acceleration of knowledge.
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Found 25 Results

A pharmacogenetic pipeline for Charcot-Marie-Tooth Disease

2021

Dr. Alex Parker
Centre Hospitalier de l'Université de Montréal, Montreal, Quebec

Lead investigator

Dr. Alex Parker

Dr. Alex Parker
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec

Budget: $30,000

Disorders: Charcot-Marie-Tooth Disease

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Neuromuscular disorders are a large group of diseases that affect the proper functioning of muscles. With the revolution in gene discovery for these disorders, and the prohibitively long time needed to develop accurate mammalian models for each new variant discovered, simpler animal models are needed to bridge the gap and help guide the development of higher models. Dr. Parker’s team uses the nematode C. elegans with its powerful genetics and rapid behavioural methodologies to model aspects of human neurodegenerative diseases. Charcot-Marie Tooth (CMT) disease is a hereditary peripheral motor and sensory neuropathy, and many of the genes involved are conserved throughout evolution. Dr. Parker’s team has developed a high throughput in vivo drug screening platform using C. elegans that has led to clinical trials for human neurodegenerative diseases. Here Dr. Parker’s team are now developing C. elegans models for CMT to be used for drug discovery and development.


Enhancing the efficacy of antisense oligonucleotide therapy for FSHD

2021

Dr. Toshifumi Yokota
University of Alberta, Edmonton, Alberta

Lead investigator

Dr. Toshifumi Yokota

Dr. Toshifumi Yokota
University of Alberta
Edmonton, Alberta

Collaborators & Co-Investigators

  • Pieter Cullis, PhD
  • Dominik Witzigmann, PhD

Research Sites & Affiliations

  • University of British Columbia, Vancouver, British Columbia

Budget: $60,000

Disorders: Facioscapulohumeral muscular dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common kinds of muscular dystrophy. It is a genetic problem that results in weakening and wasting of muscle in the face, shoulders, and limbs. FSHD is equally common in women and men. It can start at different ages, but most people with FSHD begin to show symptoms as teenagers. A childhood form of FSHD starts as early as 10 years of age—this type of FSHD is much more severe, with a high risk of patients developing problems with hearing and vision. Once FSHD starts, people with it experience a lifetime of disability. There is currently no cure for FSHD. Our proposed research aims to develop a new treatment for FSHD. FSHD is caused by abnormal production of a protein called DUX4 in muscle cells. Healthy muscle cells do not have DUX4. We plan on using small-DNA-like molecules called gapmers to decrease the amount of DUX4 protein in muscle cells. Gapmers are able to do this by specifically finding and destroying the gene products responsible for making DUX4. In addition, we will use lipid nanoparticles (LNPs) to enhance the effectiveness of gapmers. The ultimate result of this work will be to identify a possible gapmer-LNP that can be tested in clinical trials for treating FSHD. Developing a new therapy for FSHD will positively impact the lives of people with the disease.


Human iPSC-derived neurons as a model of congenital myotonic dystrophy type 1

2021

Dr. Mohamed Chahine
Université Laval, Quebec City, Quebec

Lead investigator

Dr. Mohamed Chahine

Dr. Mohamed Chahine
Université Laval
Quebec City, Quebec

Collaborators & Co-Investigators

  • Dominic Jauvin, MSc
  • Jack Puymirat MD, PhD

Research Sites & Affiliations

  • Université Laval, Quebec City, Quebec

Budget: $59,987.20

Disorders: Myotonic Dystrophy

Research Areas: Understand Diagnosis and Disorder Progression

Abstract: 

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy found in adults and currently there is no cure for this disease. DM1 is a multisystemic disease that affects several tissues including skeletal muscles, heart and brain. There are two major clinical manifestations of DM1: the classical adult form and congenital/childhood form. While the causes for skeletal muscle abnormalities in adulthood DM1 are established, the mechanisms responsible for the brain aspects of the congenital/childhood forms of DM1 remain largely unknown. The congenital form of DM1 is maternally transmitted and is characterized by reduced fetal movements, severe hypotonia and weakness at birth, often-respiratory insufficiency, feeding difficulties and talipes. Recent advances in stem cell technology now, will allow establishing stem cell lines from patients with adult and CDM1/childhood forms of the disease with the possibility to guide the differentiation of these stem cells into brain cells. Using the latest technology in disease modeling using 2 and 3D neuronal cultures), will speed up new discoveries on how we can reverse brain abnormalities in these patients.

Impact: Understanding the DM1 disease mechanism will help neurologists and other healthcare providers to improve the current diagnosis, monitor the disease progression and eventually improve treatment.


Improving myoblast transplantation outcomes via pharmacological reprogramming

2021

Dr. Nadine Wiper-Bergeron
University of Ottawa, Ottawa, Ontario

Lead investigator

Dr. Nadine Wiper-Bergeron

Dr. Nadine Wiper-Bergeron
University of Ottawa
Ottawa, Ontario

Budget: $60,544

Disorders: Duchenne/Becker Muscular Dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

One way to cure Duchenne muscular dystrophy (DMD) is to use stem cells to repair muscle. These stem cells, called satellite cells, can restore dystrophin expression to DMD muscle, reversing the muscle mass loss and weakness. However, when we isolate healthy satellite cells from muscle for transplant, they change in the dish, making them less efficient at repairing muscle when transplanted and less likely to make new satellite cells in the diseased muscle. New satellite cells from donor tissue are necessary for long-term repair of DMD muscle. My lab has discovered that a protein called C/EBPbeta helps satellite cells keep their stem cell potential. Treatment of donor satellite cells with a drug called IBMX before transplantation increases C/EBPbeta levels and keeps the cells more like satellite cells, essentially reprogramming them into more potent stem cells. When transplanted into dystrophic muscle, IBMX-treated muscle cells repair better and make new muscle stem cells in mice. We propose experiments to determine if (i) IBMX-treated cells can be delivered to all the skeletal muscles of the body through the blood; (ii) IBMX-treated cells can persist long term and make muscle function better; (iii) IBMX can also improve human satellite cells for transplant. This project aims to generate strong preclinical data necessary to advance new therapies for muscle wasting diseases like Duchenne Muscular Dystrophy into the clinic.


Promoting Muscle Repair by Pharmacological Inhibition of eIF2a Dephosphorylation

2021

Dr. Colin Crist
The Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec

Lead investigator

Dr. Colin Crist

Dr. Colin Crist
The Sir Mortimer B. Davis-Jewish General Hospital
Montreal, Quebec

Collaborators & Co-Investigators

  • Jean-Philip Lumb, PhD

Research Sites & Affiliations

  • McGill University, Montreal, Quebec

Budget: $60,000

Disorders: Duchenne/Becker Muscular Dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Duchenne muscular dystrophy (DMD) is a devastating muscle disease that affects ~1 in 3500 boys. DMD is caused by the absence of dystrophin protein in skeletal muscle, leading to chronic degeneration of muscle fibres. Muscle degeneration is initially counteracted by muscle stem cell (MuSC)-dependent muscle repair. However, chronic cycles of muscle degeneration and regeneration lead to MuSC exhaustion, which precedes the onset of progressive muscle degeneration. The resulting muscle weakness severely limits mobility and ultimately respiration of patients. until they succumb to disease in their third decade of life. Therapeutic strategies to increase or ‘expand’ MuSC populations hold significant promise to both alleviate and treat DMD. Expansion of donor MuSCs, both in culture and after engraftment, will facilitate cell-based therapies for DMD. Moreover, expansion of MuSCs in a DMD patient would be expected to prevent their exhaustion and further delay progression of disease. Our team has previously identified a major regulatory pathway for protein synthesis as a pharmacological target to expand MuSCs ex vivo. We showed that inhibition of this pathway with a small molecule, named ‘Sal003’, enables MuSC expansion. We will further improve the potency of Sal003 with the overall goal to expand MuSCs within skeletal muscle, with therapeutic implications for both cell based therapies, and new strategies that slow MuSC exhaustion in DMD and potentially other muscle disease.


Safety and efficacy of a possible epigenetic therapy for FSHD muscular dystrophy

2021

Dr. Rima Al-Awar
Ontario Institute for Cancer Research, Toronto, Ontario

Lead investigator

Dr. Rima Al-Awar

Dr. Rima Al-Awar
Ontario Institute for Cancer Research
Toronto, Ontario

Collaborators & Co-Investigators

  • Davide Gabellini, PhD
  • Gunnar Schotta, PhD
  • Serpil Eraslan, PhD
  • Gabriele Siciliano, MD, PhD

Research Sites & Affiliations

  • IRCCS Ospedale , San Raffaele, Italy
  • Ludwig-Maximilians-Universität München, Munich, Germany
  • Koc University Hospital, İstanbul, Turkey
  • Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

Budget: $1,747,846

Disorders: Facioscapulohumeral muscular dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Facioscapulohumeral muscular dystrophy (FSHD) is the most prevalent muscle disease that afflicts both children and adults regardless of their gender. FSHD is caused by aberrant gain of expression of the double homeobox 4 (DUX4) gene causing toxic effects in muscle cells. Despite the consensus on the pivotal role of DUX4 and several clinical trials, there is currently no cure or an effective therapeutic approach for FSHD patients. In our studies, we identified a novel regulator of DUX4 expression. Targeting this factor allows to block DUX4 expression and rescues the pathogenic behavior of muscle cells from FSHD patients. The treatment is safe to healthy muscle cells. Based on our results, we will use cellular and animal models of the disease to investigate a novel pharmacological approach that could represent a promising therapeutic option for FSHD patients.


Targeting defective stem cells in a preclinical model of DM1

2021

Dr. Nicolas Dumont
Hospitalier Universitaire Sainte-Justine, Montreal, Quebec

Lead investigator

Dr. Nicolas Dumont

Dr. Nicolas Dumont
Hospitalier Universitaire Sainte-Justine
Montreal, Quebec

Collaborators & Co-Investigators

  • Élise Duchesne, PhD
  • Christian Beausejour, PhD

Research Sites & Affiliations

  • Universite du Quebec a Chicoutimi, Chicoutimi, Quebec
  • CHU Sainte-Justine, Montreal, Quebec

Budget: $60,000

Disorders: Myotonic Dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Myotonic dystrophy type 1 is one of the most frequent genetic muscle diseases in humans. The disease is characterized by muscle weakness and atrophy. Moreover, the regenerative capacity of muscle stem cells, the engine of muscle repair, is reduced in the disease. Therefore, there is a high therapeutic potential for strategies targeting muscle stem cells in myotonic dystrophy type 1; however, this avenue remains unexplored. Our goal is to investigate a new therapeutic strategy aiming to target defective muscle stem cells and restore their regenerative potential. To do so, we will use a preclinical animal model of myotonic dystrophy type 1 to validate the efficacy of these novel therapeutic molecules on muscle regeneration and physical function. Improving muscle regeneration could help to mitigate disease progression and improve the quality of life of the patients. Overall, this project will explore a novel therapeutic avenue for patients that currently have limited therapeutic options.


A multidimensional single-cell approach to understand muscle dystrophy

2020

Dr. Michael Rudnicki
Ottawa Hospital Research Institute, Ottawa, Ontario

Lead investigator

Dr. Michael Rudnicki

Dr. Michael Rudnicki
Ottawa Hospital Research Institute
Ottawa, Ontario

Collaborators & Co-Investigators

  • Dr. Alessio Bava PhD
  • Fabien Le Grand, PhD
  • Stefano Previtali MD, PhD
  • Markus Rüegg PhD

Research Sites & Affiliations

  • UMR 3348 CNRS/Institut Curie/Université Paris Sud, Paris, France
  • UMRS974, Centre de Recherche en Myologie, Paris, France
  • IRCCS Ospedale, San Raffaele, Italy
  • University of Basel, Biozentrum, Basel, Switzerland

Funding partners: CIHR-Inst Genetics ,  European Rare Disease Network

Budget: $450,000

Disorders: Duchenne/Becker Muscular Dystrophy ,   Congenital Muscular Dystrophies

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Duchenne Muscular Dystrophy (DMD) and LAMA2-related Muscular Dystrophy (LAMA2 MD) are rare and devastating genetic disease of childhood manifested by progressive skeletal muscle wasting and ultimately death. In both diseases, muscle undergoes constant cycles of degeneration-regeneration exacerbated by intrinsic muscle stem cell (MuSC) dysfunction and their impaired ability to support long-term regeneration. The overall goal of the project is to use a combination of single-cell transcriptomics (RNA-sequencing) and proteomics (mass cytometry, CyTOF) to define the cellular composition of diseased muscle tissues at the single-cell resolution. We will delineate the different cell populations that pre-exist and arise during disease progression and classify the novel cellular subsets involved in this process.

This data, in combination with genetic lineage tracing will allow reconstruction of the MuSC lineage hierarchy. We will further characterize cellular subpopulations associated with human muscle dystrophies by performing 3-Dimensional intact-tissue RNA sequencing on patient biopsies. The unbiased elucidation of the cellular events underlying the different steps of muscle disease progression at the single-cell level represents crucial missing information, which will push forward our current knowledge on muscle dystrophies. Ultimately, our goal is to develop new biomarkers and eventually new pharmacological approaches to enhance therapy by stimulating intrinsic muscle tissue repair and capitalize on our single cell expertise to uncover disease-related subsets in human biopsies.


A Virtual Transition Intervention for Children and Adults Transitioning To Home Ventilation in Ontario: A Pragmatic Randomized Controlled Trial

2020

Dr. Reshma Amin
Hospital for Sick Children, Toronto, Ontario

Lead investigator

Dr. Reshma Amin

Dr. Reshma Amin
Hospital for Sick Children
Toronto, Ontario

Collaborators & Co-Investigators

  • Dr. Louise Rose
  • Dr. Andrea Sara Gershon
  • Ms. Francine Buchanan
  • Mrs. Regina Pizzuti
  • Dr. Bhatia Rajan
  • Dr. Jackie Chiang
  • Dr. Palma Cornejo
  • Dr. F Daniel
  • Dr. Katie N Dainty
  • Dr. Ian M Fraser
  • Roger S Goldstein
  • Dr. Sherri L Katz
  • Dr. David J Leasa
  • Dr. Audrey Lim
  • Dr. Sandra M McKay
  • Dr. Douglas Mckim
  • Dr. Myla Moretti
  • Dr. Mika L Nonoyama
  • Dr. Aman Sidhu
  • Dr. Anu Tandon
  • Dr. Brenda E Toonders
  • Dr. Kevin M Workentin

Research Sites & Affiliations

  • Hospital for Sick Children, Toronto, Ontario

Funding partners: CIHR – Inst of Human Development & Child & Youth ,  CIHR – Inst of Health Services & Policy Research ,  CIHR – Major Initiatives SPOR/CE

Budget: $1,013,813

Disorders: All Neuromuscular Disorders

Research Areas: Enhance Care

Abstract: 

The number of people that use a ventilator (a machine that supports breathing) at home is increasing in Canada and around the world. These individuals have complex health problems, require a lot of care and they use the healthcare system often. Unfortunately, the care for individuals using mechanical ventilators isn’t coordinated which results in frequent visits to the hospital and stress on the patient and family. Virtual care is a way to improve healthcare for individuals using ventilators. Virtual care is a good idea for individuals using ventilators because it can bring “the right people with the right expertise at the right time” into the homes of these complex patients. A newly developed virtual care platform called aTouchAway™ is now developed. It is sophisticated enough to meet the needs of individuals using ventilators and their care needs. This study will test a virtual care intervention using the aTouchAway™ platform for children and adults newly going home with ventilators in Ontario, Canada. We are studying the effect on the following: visits to the Emergency Department, patient and families’ experience and if they like using it, the costs on the healthcare system and healthcare provider time and if they like using the intervention. We have worked closely with individuals using ventilators at home and their families to design this study and make sure the results are important to them. Our study is testing a promising virtual care intervention for individuals newly going home with ventilators. Our results will help to improve the quality of life for individuals using ventilators at home by making their healthcare better.


Impact: 

See Dr Amin’s Video about the Project on MDC’s Let’s Talk NMD Series.

Canonical disease features in a novel mouse model of SMA type III and IV

2020

Dr. Rashmi Kothary
Ottawa Hospital Research Institute, Ottawa, Ontario

Lead investigator

Dr. Rashmi Kothary

Dr. Rashmi Kothary
Ottawa Hospital Research Institute
Ottawa, Ontario

Collaborators & Co-Investigators

  • Aoife Reilly
  • Ariane Beauvais, M.Sc.

Research Sites & Affiliations

  • Ottawa Hospital Research Institute, Ottawa, Ontario

Budget: $100,000

Disorders: Spinal Muscular Atrophy

Research Areas: Understand Diagnosis and Disorder Progression

Abstract: 

Current research in spinal muscular atrophy (SMA) focuses primarily on severe patients and on severe pre-clinical models. It is important to also cater research to milder patients who are already living with the disorder. Mild SMA has been challenging to model in mice for reasons that are not altogether clear. Therefore, a clear need exists in the field for a model to study the mild forms of the disease (SMA type III/IV). This proposal aims to characterize a novel mouse model generated in our laboratory to help study defects in mild SMA patients. It will allow for better characterization of molecular changes within skeletal muscle and motor neurons, and determine whether these differ in any way to those identified in the models of more severe SMA. The work will also assess whether biomarkers identified for the severe form of the disease will be useful in mild SMA.

This new model will allow for the understanding of the most susceptible pathogenic molecular changes in motor neurons, and investigation of the effects of SMN depletion in milder forms of the disease. In addition, it will also provide guidance for the currently aging SMA patient population treated with anti-sense oligonucleotides or gene therapy.

Collectively, the proposed studies will substantially inform the diagnosis, biology and treatment of mild SMA.


CRISPR mediated gene editing: a novel therapeutic strategy for nemaline myopathy

2020

Dr. James Dowling
The Hospital for Sick Children, Toronto, Ontario

Lead investigator

Dr. James Dowling

Dr. James Dowling
The Hospital for Sick Children
Toronto, Ontario

Collaborators & Co-Investigators

  • Henk Granzier, PhD
  • Ronald Cohn, MD
  • Hernan Gonorazky, MD

Research Sites & Affiliations

  • University of Arizona, Tempe, Arizona
  • The Hospital for Sick Children, Toronto, Ontario

Budget: $100,000

Disorders: Hereditary Myopathies

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Nemaline myopathy (NM) is a severe disorder associated with muscle weakness that results in impairments in motor functions such as mobility, speech and eating. Genetic changes also called mutations in at least 10 genes are known to cause NM, with changes in the NEB gene the most common cause. Despite advancing knowledge of what causes the disease and how these causes affect muscle function, there are currently no therapies. Genome editing with the CRISPR Cas9 system is revolutionizing science and also holds great potential as a strategy for treating genetic disease. NM is an ideal candidate disease for CRISPR based gene editing as most of the gene mutations that cause it are well known and restoring the normal working of the mutated gene should result in functional and clinical improvements. This research project aims to use the CRISPR system to correct the NEB exon 55 deletion mutation, the most common single mutation associated with NM, by re-introducing exon 55. So far preliminary data shows NEB exon 55 can be reintroduce into patient muscle cells and thereby restore NEB RNA and protein. Based on these data, the group will examine this therapeutic approach in a mouse model of NM to test if they can restore Nebulin in a living animal and whether such restoration rescues disease in this model. This is a critical study that is essential for developing this strategy for patients.

If successful, it will represent a first potential therapy for NM. The approach will also provide a road map for developing similar approaches for other NM subtypes.


Empowering caregivers to better manage DM patients’ neurobehavioral symptoms

2020

Dr. Benjamin Gallais
Cégep de Jonquière, Jonquière, Quebec

Lead investigator

Dr. Benjamin Gallais

Dr. Benjamin Gallais
Cégep de Jonquière
Jonquière, Quebec

Collaborators & Co-Investigators

  • Dr. Cynthia Gagnon Ph.D
  • Dr. Luc Laberge, Ph.D.

Research Sites & Affiliations

  • Université de Sherbrooke, Sherbrooke, Quebec
  • Cégep de Jonquière, Jonquière, Quebec

Budget: $47,600

Disorders: Myotonic Dystrophy

Research Areas: Enhance Care

Abstract: 

Myotonic dystrophy type 1 (DM1) amongst others includes symptoms like excessive fatigue and sleepiness, lack of motivation, peculiar personality traits and cognitive deficits including organization, decision-making, and interpersonal difficulties. All these features greatly affect an individual’s daily living autonomy, health management as well as individuals’ and caregivers’ social participation. Furthermore, misunderstanding of these unapparent symptoms often bring family and social conflicts. Briefly, most DM-patients and caregivers highlight these neurobehavioral symptoms than the muscular symptoms that are the hallmark of the condition. This project aims to develop and transfer information and practical advices into numeric educational materials to support caregivers regarding neurobehavioral symptoms of DM1. These products would take the form of guides, video capsules and cartoons. The innovative aspect of this project lies on the fact that products will be based on challenging day-to-day life situations experienced by patients and caregivers called “partners”, as they are part of the research team in all study steps. A better understanding/management of neurobehavioral symptoms through personalized multimedia products using patients and caregivers’ experience may improve the patient-caregiver relationship, provide a greater and longer patients’ autonomy, and increase social participation.


Identification of modifiers underlying the variable phenotypes of RYR1 myopathy

2020

Dr. Martine Tétreault
Centre Hospitalier de l’Université de Montréal, Montreal, Quebec

Lead investigator

Dr. Martine Tétreault

Dr. Martine Tétreault
Centre Hospitalier de l’Université de Montréal
Montreal, Quebec

Collaborators & Co-Investigators

  • Dr. Cam-Tu Nguyen, MD
  • Dr. Benjamin Ellezam, MD, PhD
  • Dr. Jean-Denis Brisson, MD

Research Sites & Affiliations

  • CHU Sainte-Justine, Montreal, Quebec
  • Hôpital de Chicoutimi, Chicoutimi, Quebec

Budget: $100,000

Disorders: Hereditary Myopathies

Research Areas: Understand Diagnosis and Disorder Progression

Abstract: 

Variability in the characteristic symptoms of a disorder or phenotype is observed in many diseases and neuromuscular disorders are not an exception. In many cases the spectrum of how these disorders present is an obstacle to our understanding the causes and thus is hindering the development of valuable treatments. RYR1-related disorders are a good example of extremely variable neuromuscular disorders with phenotype ranging from a severe neonatal myopathy to malignant hyperthermia susceptibility. Our study cohort, composed of individuals carrying the same novel RYR1 heterozygous missense variant and extremely diverse phenotype, represents a unique and powerful example of the variable expressivity associated with RYR1 mutations. This cohort is therefore ideal for investigating the molecular causes of this phenomenon. We are proposing to look at transcriptomic and epigenomic signatures that could be associated with variability.

Our findings will hold the potential to improve diagnosis, help evaluate disease progression, offer a better risk management to patients and ultimately lead to new therapeutic avenues.


Muscle strength reference values for adults: a critical need in NMD

2020

Dr. Luc Hébert
Université Laval, Quebec City, Quebec

Lead investigator

Dr. Luc Hébert

Dr. Luc Hébert
Université Laval
Quebec City, Quebec

Collaborators & Co-Investigators

  • Dr. Elise Duchesne PT, PhD
  • Dr. Cynthia Gagnon OT, PhD
  • Dr. Bernard Brais, MD, PhD
  • Émilie Petitclerc PT, M.Sc.
  • Marie-Pier Rousse MPT, M.Sc.
  • Marc Perron PT, M.Sc.

Research Sites & Affiliations

  • Université du Québec à Chicoutimi, Chicoutimi, Quebec
  • Université de Sherbrooke, Sherbrooke, Quebec
  • McGill University, Montreal, Quebec
  • Université Laval, Quebec City, Quebec

Budget: $97,406.67

Disorders: All Neuromuscular Disorders

Research Areas: Enhance Care

Abstract: 

Maximal muscle strength (MMS) is a key measure of how well a person’s muscles are working People affected by neuromuscular disorders have weaken muscle strength amongst others. Moreover, in some types of NMDs like myotonic dystrophy type 1 we have shown that strength training leads to lasting improvements in muscle strength (Roussel 2019). In order to be able to know if a person’s maximal muscle strength is “normal” we need a comparison or reference chart of what would be expected of a healthy individuals of similar age, sex, weight and height. This chart will be necessary to identify muscle weakness in order to accurately measure changes overtime and treatment efficacy. To develop this chart this research team will use standardized protocols using high quality, accessible and user-friendly handheld dynamometers (HHD) which can measure in clinic , rapid, accurate, valid, reliable and sensitive MMS value of 300 healthy participants (30 men/30 women in each decade from 18 to 69) using a standardized HHD protocol In addition to provide descriptive statistics of MMSs, predictive equation models will be established from data collected, which will allow clinicians to compare MMS measured to the expected MMS values for the same age and sex.

Such reference values will allow documenting muscle strength changes, assessing intervention effectiveness and guide prognosis in order to optimize healthcare for people living with NMD.


NMD4C: An integrated research network for patients, scientists, and clinicians to improve outcomes and access to therapies for patients with neuromuscular disorders in Canada

2020

Dr. Hanns Lochmuller
The Children’s Hospital of Eastern Ontario, Ottawa, Ontario

Lead investigator

Dr. Hanns Lochmuller

Dr. Hanns Lochmuller
The Children’s Hospital of Eastern Ontario
Ottawa, Ontario

Collaborators & Co-Investigators

  • Dr. James Dowling
  • Dr. Jodi Warman Chardon
  • Dr. Rashmi Kothary
  • Ms. Stacey Lintern
  • Dr. Bernard Brais
  • Dr. Craig Campbell
  • Dr. Cynthia Gagnon
  • Dr. Daria Wojtal
  • Dr. Homira Osman
  • Dr. Hugh McMillan
  • Dr. Kathryn Selby
  • Dr. Lawrence Korngut
  • Dr. Maryam Oskoui
  • Dr. Reshma Amin
  • Ms. Nicola Worsfold
  • Ms. Teresa Buffone
  • Dr. Aaron Izenberg
  • Ms. Bonnie Wooten
  • Dr. Hernan Gonorazky
  • Dr. Jason Karamchandani
  • Mr. Joshua Lounsberry
  • Ms. Kim Amburgey
  • Ms. Patricia Mortenson
  • Mr. Perry Esler
  • Ms. Rhiannon Hicks
  • Ms. Rochelle ten Haaf
  • Dr. Valérie Gagné-Ouellet
  • Dr. Victoria Hodgkinson

Research Sites & Affiliations

  • , ,

Funding partners: CIHR – Inst of Musculoskeletal Health and Arthritis

Budget: $1,200,000

Disorders: All Neuromuscular Disorders

Research Areas: Amplify Research & Accelerate Knowledge

Abstract: 

The Neuromuscular Disease Network for Canada (NMD4C) is the new pan-Canadian network that brings together the country’s leading clinical, scientific, technical, and patient expertise to improve care, research, and collaboration in neuromuscular disease.

The goals of the new NMD4C network are to:

  • Build and sustain a new network of neuromuscular disorders stakeholders to make it easier for Canadian researchers, clinicians and patient advocates to improve research and care.
  • Train and educate the next generation of neuromuscular disorder-specific clinicians, scientists, and patient advocates to improve the quality of care and research.
  • Raise the standard of care for neuromuscular disorders and access to therapies across Canada, by developing and providing the right information, to the right audience, at the right time.
  • Expand access to research resources and build research capacity by uniting local efforts across Canada and linking to international activities.
Further Information:

About the Neuromuscular Disease Network for Canada
NMD4C propelling research forward for patients, scientists and clinicians


Patient preferences in treatments for myasthenia gravis: a DCE experiment

2020

Dr. Carolina Barnett Tapia
University Health Network, Toronto, Ontario

Lead investigator

Dr. Carolina Barnett Tapia

Dr. Carolina Barnett Tapia
University Health Network
Toronto, Ontario

Collaborators & Co-Investigators

  • Dr. Ahmed Bayoumi MD, MSc

Research Sites & Affiliations

  • St. Michael’s Hospital, Toronto, Ontario

Budget: $69,100

Disorders: Myasthenia Gravis

Research Areas: Enhance Care

Abstract: 

Myasthenia Gravis (MG) is a rare condition where individuals impacted experience muscle weakness. This can affect their arms and legs, but also the muscles needed for eating, speaking and breathing, with the risk of dying. With modern treatments, individuals with MG have better health outcomes and reduced risk of death; However, despite current treatments, only 1 in 5 patients are completely symptom-free.

The goal of treatment is to achieve a minimal amount of symptoms with as little side effects as possible. The problem is that currently, we define minimal symptoms and tolerable side effects based on physicians’ and experts’ opinions. We know from other disorders that clinicians’ and patients’ views are often different; however, the preferences of people with myasthenia have not been studied. Given the increasing number of new treatments that are becoming available for this disease, it is important to understand how their use in routine care will improve outcomes that are relevant to patients.

In this project, we will study how people living with MG make decisions regarding new interventions (potential treatments, surgeries etc.), considering the trade-offs between potential side effects, efficacy, and accessibility. We will compare the views of individuals with MG to the views of the physicians who treat them. This study will also serve as a model for other neuromuscular diseases, to understand how patients make decisions regarding new interventions.


Profiling granzymes in inflammatory neuromuscular diseases

2020

Dr. David Granville
University of British Columbia, Vancouver, British Columbia

Lead investigator

Dr. David Granville

Dr. David Granville
University of British Columbia
Vancouver, British Columbia

Collaborators & Co-Investigators

  • Michael Berger MD, PhD

Research Sites & Affiliations

  • University of British Columbia, Vancouver, British Columbia

Budget: $100,000

Disorders: Immune-Mediated Myopathies (Myositis) ,   Chronic Inflammatory demylinating polyneuropathy ,   Myasthenia Gravis

Research Areas: Understand Diagnosis and Disorder Progression

Abstract: 

One group of neuromuscular disorders are caused by inflammation, which is the body’s response to injury or external threats, like bacteria or viruses. An abnormally elevated inflammatory response, however, can result in an attack on the body’s own muscle and/or nerve cells, disrupting their normal function. Presently, individuals with inflammatory neuromuscular disease are subjected to non-specific, ineffective treatments with considerable side effects. The goal of our proposal is to identify novel, disease-modifying therapeutic targets that offer a safer, more effective alternative to alleviate disease symptoms. Granzymes are proteins that are key to the body’s normal inflammatory response. This team of scientists and physicians have shown that these granzymes are active and found at elevated levels in many inflammatory and autoimmune diseases, like skin diseases, asthma, lupus, and multiple sclerosis. Recently, other researchers have found preliminary evidence that granzymes can also be detected at high levels in some neuromuscular disease patients. In our current proposed project, we aim to comprehensively examine 3 different types of inflammatory muscular diseases to assess their granzyme levels, and their relationship to disease severity. These are Inflammatory myopathies; (Myositis; Polymositis, dermatomyositis; inclusion-body myositis); Chronic inflammatory demyelinating polyneuropathy, and Myasthenia gravis.

This study will allow us to better understand if novel therapies can be designed against granzymes to alleviate the symptoms of inflammatory neuromuscular disease.


Reverse translation from the diabetes clinic to pre-clinical muscular dystrophy

2020

Dr. Vladimir Ljubicic
McMaster University, Hamilton, Ontario

Lead investigator

Dr. Vladimir Ljubicic

Dr. Vladimir Ljubicic
McMaster University
Hamilton, Ontario

Budget: $100,000

Disorders: Duchenne/Becker Muscular Dystrophy ,   Myotonic Dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

A critical, unmet clinical need is the identification of effective therapies for Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). When a protein in our muscles called AMP-activated protein kinase (AMPK) is turned on, it reduces disease severity in mice with DMD and DM1. However, AMPK-activating drugs in previous muscular dystrophy studies are neither safe for long-term human use, nor particularly potent. The use of better compounds to activate AMPK, those that are safe, effective, and able to be taken orally, would greatly increase their clinical impact for DMD and DM1 patients. Here, we will employ a new strategy to target AMPK for the treatment of muscular dystrophy. Specifically, we will investigate whether stimulation of AMPK with a practical, next-generation compound improves the health of mice with DMD and DM1, which would provide a better outlook for applicability in muscular dystrophy patients. We will focus on the ability of the AMPK-activating drug to restore the proper structure and function of dystrophic muscles, as well as explore the molecular mechanisms of its action. There is no better time than the present to perform this study since this drug is in clinical trials for treating diabetes. This proposal will determine the therapeutic potential of a novel AMPK-stimulating compound for the most prevalent muscular dystrophies in children and adults in Canada.


Therapeutic potential of CK1 agonists in inherited peripheral neuropathies

2020

Dr. Benoit Gentil
McGill University, Montreal, Quebec

Lead investigator

Dr. Benoit Gentil

Dr. Benoit Gentil
McGill University
Montreal, Quebec

Collaborators & Co-Investigators

  • Rami Massie MD

Research Sites & Affiliations

  • The Royal Institution for the Advancement of Learning, McGill University, Montreal, Quebec

Budget: $100,000

Disorders: Charcot-Marie-Tooth Disease ,   Giant Axonal Neuropathy ,   Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay?

Research Areas: Understand Diagnosis and Disorder Progression

Abstract: 

Genetic changes or mutations in the NEFL gene cause severe pediatric forms of Charcot-Marie-Tooth disease type 2E. Recent progresses of genetics points to an increasing contribution of genes involved in neurofilaments (NF) homeostasis as a cause of Hereditary Motor Sensory Neuropathies (HMSN). The NF network provides an excellent biomarker for the development of therapies targeting the mechanism of sensory motor degeneration. Kinases, small molecules in our bodies, like the casein kinase 1 (CK1), play a crucial role in the complex assembly process of NFs and our preliminary data point to a role of CK1 in the development (or )of these HMSN. Our proposal aims to determine the role of CK1 in the pathogenesis of HMSN and the therapeutic potential of a brain permeant CK1 agonist.

We aim:

1) To demonstrate that CK1 is involved in proper assembly of CMT2E-causing mutants NEFL in vitro and in vivo.

2) To demonstrate that CK1 is involved in the pathogenic cascade caused by mutations in GAN, HSPB1 and SACS in cellular models.

3) To Test the therapeutic potential of the CK1 agonist and demonstrate the proof of concept. We expect to identify the contribution of CK1 in the pathogenic cascades of these HMSN and the therapeutic potential of a CK1 agonist. The proposal includes a close collaboration with clinicians (Drs Massie, McGill university) for developing a therapy translatable to human and to identify patient’s populations who will benefit of this therapy.


A better trunk and lower limb control for a better mobility: Assessment of a re-entrainment program in Autosomal recessive spastic ataxia of Charlevoix-Saguenay

2019

Dr. Cynthia Gagnon
École de réadaptation CIUSSS du Saguenay-Lac-St-Jean, Jonquière, Quebec

Lead investigator

Dr. Cynthia Gagnon

Dr. Cynthia Gagnon
École de réadaptation CIUSSS du Saguenay-Lac-St-Jean
Jonquière, Quebec

Collaborators & Co-Investigators

  • Isabelle Lessard, BSc (PT)

Research Sites & Affiliations

  • Universite de Sherbrooke, Sherbrooke, Quebec

Budget: $40,639.65

Disorders: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay?

Research Areas: Enhance Care

Abstract: 

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a hereditary neurological disorder presenting with pyramidal (i.e. lower limbs spasticity), cerebellar (i.e. incoordination) and neuropathic (i.e. distal muscle weakness) impairments. Our previous research studies have shown that people with ARSACS have major impairments in regard to upper and lower limbs coordination, upper limbs dexterity, walking speed/endurance and balance control, ultimately leading to participation restrictions and difficulty to perform activities of daily living. No cure exists for ARSACS; at the moment we can only alleviate deficits. Some study conducted in degenerative ataxia other than ARSACS have documented positive effects of physical therapy on balance, gait and performance of daily living activities. However, currently, there is limited knowledge about rehabilitation interventions for ARSACS.

The objective of this pilot project is to document the effects of a re-entrainment program aiming to increase trunk and lower limb motor control on walking capacities, balance and accomplishment of daily activities in people with ARSACS.


A Population-based Cohort Study of Pregnancy Outcomes in Women with Myasthenia Gravis

2019

Dr. Ari Breiner
Ottawa Hospital Research Institute, Ottawa, Ontario

Lead investigator

Dr. Ari Breiner

Dr. Ari Breiner
Ottawa Hospital Research Institute
Ottawa, Ontario

Collaborators & Co-Investigators

  • Steven Hawken, PhD
  • Carolina Barnett-Tapia, MD, PhD
  • Pierre Bourque, MD
  • Jodi Warman-Chardon, MD, MSc

Research Sites & Affiliations

  • Ottawa Hospital Research Institute, Ottawa, Ontario
  • University of Toronto, Toronto, Ontario
  • University of Ottawa, Ottawa, Ontario

Budget: $ 49,851.00

Disorders: Myasthenia Gravis

Research Areas: Enhance Care

Abstract: 

There is little in the medical literature to guide the management of pregnant patients with myasthenia gravis (MG). Existing guides are based on small series and expert opinion, rather than population-based or prospective data.

Objective: To determine if pregnant MG patients are at increased risk of perinatal compilation (including fetal and maternal complications), in comparison with healthy controls matched on age, geographic region, and year. Month of delivery.

Study Design Retrospective, population-based, cohort study using administrative health databases housed at ICES (Institute for Clinical Evaluative Sciences).

Significance: This study provides a unique opportunity to study a relatively rare disease using province-wide health services data. The results of the study should both inform clinical practice and form the basis of future prospective studies.


Denosumab for the Treatment of Osteoporosis in Boys with Duchenne Muscular Dystrophy: A Pilot Study

2019

Dr. Leanne M. Ward
Children's Hospital of Eastern Ontario, Ottawa, Ontario

Lead investigator

Dr. Leanne M. Ward

Dr. Leanne M. Ward
Children's Hospital of Eastern Ontario
Ottawa, Ontario

Collaborators & Co-Investigators

  • Jerome Frenette, MScPT, PhD
  • Laura McAdam MSc, MD
  • Marie-Eve Robinson MD, C.M. MSc

Research Sites & Affiliations

  • Universite Laval, Quebec City, Quebec
  • University of Toronto, Toronto, Ontario
  • Children's Hospital of Eastern Ontario, Ottawa, Ontario

Budget: $49,596.00

Disorders: Duchenne/Becker Muscular Dystrophy

Research Areas: Enhance Care

Abstract: 

Boys with glucocorticoid (GC)-treated Duchenne muscular dystrophy (DMD) are at risk for vertebral and long bone fractures due to osteoporosis. Vertebral fractures in DMD cause chronic back pain and spine deformity, while leg fractures can lead to premature, permanent loss of ambulation. Prevalence studies have shown that 20-60% of boys will sustain long bone fractures and up to 30% will have painful vertebral fractures. Fractures have also been linked in DMD to fat embolus syndrome causing acute respiratory distress and sudden death. The goal of this study, a pilot trial, is to evaluate the safety and feasibility of a novel therapy in the treatment of osteoporosis (denosumab) compared to our standard of care approach (intravenous bisphosphonate therapy, zoledronic acid) in boys with DMD. Denosumab is a human monoclonal antibody that inactivates RANKL, thereby inhibiting bone resorption and increasing bone strength at both trabecular (spine) and cortical (long bone) sites. A large study on close to 8,000 women with post-menopausal osteoporosis (the FREEDOM trial) showed that denosumab reduced vertebral and hip fracture risks without an increased frequency of side effects compared to placebo. The use of this agent is particularly compelling in the DMD setting, since studies in a murine model of DMD by co-investigator J. Frenette have shown that RANKL inhibition protects against DMD muscle dysfunction, degeneration and inflammation.

 


Exosomal Delivery of Wnt7a for treating Duchenne Muscular Dystrophy

2019

Dr. Michael Rudnicki
Ottawa Hospital Research Institute, Ottawa, Ontario

Lead investigator

Dr. Michael Rudnicki

Dr. Michael Rudnicki
Ottawa Hospital Research Institute
Ottawa, Ontario

Funding partners: Jesse’s Journey

Budget: $300,000

Disorders: Duchenne/Becker Muscular Dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Duchenne Muscular Dystrophy is a devastating genetic disorder manifested by progressive muscle wasting and ultimately death around the second decade of life. Injection of a secreted protein called Wnt7a greatly enhances muscle regeneration resulting in amelioration of dystrophic progression. However, based on the its chemical nature Wnt7a cannot be delivered via the blood circulation. We have discovered that Wnt7a is normally secreted on the surface of small vesicles called exosomes during muscle regeneration.

Exosomes have been demonstrated to effectively deliver cargo through the circulation to muscle. We will compare the activity of free Wnt7a versus exosomal Wnt7a, we will investigate the mechanism that targets Wnt7a to exosomes, and we will test the ability of exosomal Wnt7a to be delivered to muscle through the circulation. These experiments have the potential to significantly increase the efficacy of Wnt7a for treating Duchenne Muscular Dystrophy, especially when used in combination with gene correction therapies.


Interventional Study of Expiratory Muscle Strength Training as a Treatment for Muscle Disease

2019

Dr. Gerald Pfeffer
University of Calgary, Calgary, Alberta

Lead investigator

Dr. Gerald Pfeffer

Dr. Gerald Pfeffer
University of Calgary
Calgary, Alberta

Collaborators & Co-Investigators

  • Lawrence Korngut MD, Msc
  • Stephanie Plamondon, MD
  • Aneal Khan, MD
  • Andrea Loewen, MD
  • Karen Rimmer, MD
  • Curtis Dumonceaux, RRT
  • Ashley Waito, SLP

Research Sites & Affiliations

  • University of Calgary, Calgary, Alberta
  • University of Toronto, Toronto, Ontario

Budget: $47,837.98

Disorders: Hereditary Myopathies

Research Areas: Enhance Care

Abstract: 

Genetic muscle diseases are a heterogeneous group of disorders, that for the greater part, do not currently have any disease-modifying therapies. Many of these conditions cause abnormal swallowing and/or ventilatory function, which has a major effect on quality of life, morbidity, and mortality. Expiratory muscle strength training (EMST) is a rehabilitative approach that can be performed using a handheld device, that provides a customisable amount of resistance to expiration. It is customisable to individual needs, and has preliminary evidence in other neurodegenerative conditions showing it can result in improved swallowing and respiratory function. It has not yet been studied in patients with hereditary muscle diseases.
The objective is to perform an open-label, interventional study of 20 participants with hereditary muscle disease, who have respiratory and/or swallowing impairment. Obtain preliminary data indicating whether EMST has benefit for respiratory/swallowing function.


Non-viral, immune-modulatory nanoparticles for delivery of CRISPR/Cas9 as a treatment intervention for Duchenne Muscular Dystrophy

2019

Dr. Anthony Gramolini
University of Toronto, Toronto, Ontario

Lead investigator

Dr. Anthony Gramolini

Dr. Anthony Gramolini
University of Toronto
Toronto, Ontario

Collaborators & Co-Investigators

  • Ronald Cohn, MD

Research Sites & Affiliations

  • The Hospital for Sick Children, Toronto, Ontario

Funding partners: Jesse’s Journey

Budget: $300,000

Disorders: Duchenne/Becker Muscular Dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

We are developing non-viral vehicles for delivery of genome editing machinery with specific emphasis on targeting skeletal muscle cells associated with Duchenne muscular dystrophy (DMD). Clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9) is a powerful new gene editing tool. Our objective focuses on generating novel degradable and biocompatible nanoparticles (BNPs), using our U of T patented polyurethane technology. These carriers address limitations with current CRISPR/Cas9 delivery platforms, specifically eliminating use of immune reactive virus; enables co-delivery of a specific targeting tool; and reduces potential off-target tissue damage; . Studies will evaluate the therapeutic corrective capacity of nanoparticles in a DMD mouse model, and establish a technology to enable novel therapies for DMD patients in Canada and abroad.