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

Lead Investigator: Dr.  Reshma Amin MD | Hospital for Sick Children, ON
Collaborators: Dr. Louise Rose, Dr. Andrea Sara Gershon, Mrs. Francine Buchanan, Mrs. Regina Pizzuti, et al.

Funding Period: 2019/2020 to 2022/2023
Competition: Team Grant: Transitions in Care – Stream 2 – eHIPP solutions for transitions in care gaps Grant New
In Partnership with: CIHR – Inst of Health Services & Policy Research; CIHR – Inst of Human Development &Child &Youth; CIHR – Major Initiatives SPOR/CE
Budget: $1,013,813
Disorder Area: All Neuromuscular Disorders
Research Area: Respiratory, Transitions in care

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.

Further Information:

See Dr Amin’s Video about the Project on MDC’s Let’s Talk NMD Series here
Clinical trial information


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

Lead Investigator: Dr.  Hanns Lochmuller
Steering Committee: Dr. James Dowling, Dr. Jodi Warman Chardon, Dr. Rashmi Kothary, Stacey Lintern
Investigators: The Neuromuscular Disease Network – Network participants

Funding Period: 2019/2020 to 2022/2023
Competition: CIHR – Network Catalyst Competition
In Partnership with: CIHR – Inst of Musculoskeletal Health and Arthritis
Budget: $1,200,000
Disorder Area: Cross cutting, All Neuromuscular Disorders

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


A multidimensional single-cell approach to understand muscle dystrophy

Lead Investigator: Dr. Michael Rudnicki OC, PhD, FRS, FRSC | Ottawa Hospital Research Institute, ON, CANADA
Collaborators: Dr. Alessio Bava PhD | UMR 3348 CNRS/Institut Curie/Université Paris Sud, FRANCE
Fabien Le Grand, PhD | UMRS974, Centre de Recherche en Myologie, Paris, FRANCE
Stefano Previtali MD, PhD | IRCCS Ospedale San Raffaele, ITALY
Markus Rüegg PhD | University of Basel, Biozentrum, SWITZERLAND
Competition: Team Grant: E-Rare-3 Joint Transnational Call (2019)
In Partnership with: CIHR, European Rare Disease Network, Muscular Dystrophy Canada

Funding Period: 2020-2023
Budget: $450,000
Disorder Area: Duchenne Muscular Dystrophy, LAMA2-related Muscular Dystrophy

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.


Patient preferences in treatments for myasthenia gravis: a DCE experiment

Lead Investigator: Dr. Carolina Barnett Tapia MD, PhD | University Health Network, ON
Collaborator: Dr. Ahmed Bayoumi MD, MSc | St. Michael’s Hospital, ON

Funding Period: 2020-2022
Budget: $69,100
Disorder Area: Myasthenia Gravis
Research Area: Patient preferences

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.


Empowering caregivers to better manage DM patients’ neurobehavioral symptoms

Lead Investigator: Dr. Benjamin Gallais, Ph.D. | Cégep de Jonquière , Qu
Collaborators: Dr. Cynthia Gagnon Ph.D. | Université de Sherbrooke, Qu
Dr. Luc Laberge, Ph.D. | Cégep de Jonquière, Qu

Funding Period: 2020-2022
Budget: $47,600
Disorder Area: Myotonic Dystrophy
Research Area: Cognitive and Behavioral Aspects of Neuromuscular Diseases; Quality of Life

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.


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

Lead Investigator: Dr. James Dowling, The Hospital for Sick Children
Collaborators: Dr. Henk Granzier, Ph.D. | University of Arizona, USA
Dr. Ronald Cohn, MD | The Hospital for Sick Children, ON
Dr. Hernan Gonorazky, MD | The Hospital for Sick Children, ON

Funding Period: 2020-2022
Budget: $100,000
Disorder Area: Nemaline myopathy
Research Area: Gene targeting therapy; gene editing, In vivo Models

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.


Profiling granzymes in inflammatory neuromuscular diseases

Lead Investigator: Dr. David Granville Ph.D. |University of British Columbia, BC
Collaborator: Dr. Michael Berger MD, Ph.D. | University of British Columbia, BC

Funding Period: 2020-2022
Budget: $100,000
Disorder Area: Inflammatory myopathy; (Myositis; Polymositis, dermatomyositis; inclusion-body myositis); Chronic inflammatory demyelinating polyneuropathy; Myasthenia gravis
Research Area: Biomarkers; Inflammation/ Immune Mechanisms

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.


Therapeutic potential of CK1 agonists in inherited peripheral neuropathies

Lead Investigator: Dr. Benoit Gentil Ph.D. |The Royal Institution for the Advancement of Learning/ McGill University, QU
Collaborator: Rami Massie MD |The Royal Institution for the Advancement of Learning/ McGill University, QU

Funding Period: 2020-2022
Budget: $100,000
Disorder Area: Hereditary motor and sensory neuropathies, Charcot-Marie-tooth disease, rare ataxia
Research Area: Biomarkers; Cell-Based Modeling and Screening; In vivo Models; Protein Homeostasis

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.


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

Lead Investigator: Dr. Luc Hébert PT, Ph.D, CD | Université Laval, Qu
Dr. Elise Duchesne PT, Ph.D. | Université du Québec à Chicoutimi, Qu
Dr. Cynthia Gagnon OT, Ph.D. | Université de Sherbrooke, Qu
Dr. Bernard Brais, MD, Ph.D. | McGill University, Qu
Émilie Petitclerc PT, M.Sc. | Université de Sherbrooke, Qu
Marie-Pier Rousse MPT, M.Sc. | Université du Québec à Chicoutimi, Qu
Marc Perron PT, M.Sc. | Université Laval, Qu

Funding Period: 2020-2022
Budget: $97,406.67
Disorder Area: Cross-Cutting

Research Area of focus: Biomarkers, Diagnostic tools, Outcome Measures for Neuromuscular Diseases

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.


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

Lead Investigator: Dr. Rashmi Kothary Ph.D., Ottawa Hospital Research Institute
Team: Aoife Reilly, Ottawa Hospital Research Institute
Ariane Beauvais, M.Sc., Ottawa Hospital Research Institute

Funding Period: 2020-2022
Budget: $100,000
Disorder Area: Spinal Muscular Atrophy
Research Area of focus: Biomarkers, Gene targeting therapy including gene transfer/ antisense oligonucleotides and gene editing, In vivo Models

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


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

Lead Investigator: Dr. Vladimir Ljubicic Ph.D. | McMaster University, ON

Funding Period: 2020-2022
Budget: $100,000
Disorder Area: Myotonic Muscular Dystrophy, Duchenne Muscular Dystrophy
Research Area of focus: DNA and RNA Repeat Diseases, In vivo Models, Metabolic disturbances in neuromuscular diseases, Outcome Measures for Neuromuscular Diseases, Protein Homeostasis, Regeneration and Repair

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.


Identification of modifiers underlying the variable phenotypes of RYR1 myopathy

Lead Investigator: Dr. Martine Tétreault, Ph.D. | Centre Hospitalier de l’Université de Montréal, QU
Collaborators: Dr. Cam-Tu Nguyen, MD | CHU Sainte-Justine, QU
Dr. Benjamin Ellezam, MD, Ph.D. |CHU Sainte-Justine
Dr. Jean-Denis Brisson, MD | HÔPITAL DE CHICOUTIMI

Funding Period: 2020-2022
Budget: $100,000
Disorder Area: Congential myopathies; RYR1 myopathy
Research Area of focus: Biomarkers; Diagnostic tools

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.