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:
2024
Lead investigator
Dr Keir Menzies
University of Ottawa
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $99,906.54
Disorders: All Neuromuscular Disorders (cross-cutting) , Duchenne/Becker Muscular Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Duchenne Muscular Dystrophy (DMD) is a serious disease that mainly affects boys, with about 1 in every 3,500 males being affected. Muscles from people with DMD get damaged when they contract, leading to muscle weakness. Unlike muscle from healthy individuals, the muscles can’t repair themselves properly, and this gets worse over time. Right now, there is no cure for DMD, and even the gene and cell therapies in development might not completely fix the problem. The most used treatment is a type of medication called corticosteroids. They can help people with DMD live longer, but using them for a long time can cause problems like muscle shrinking, metabolism issues, and altered hormone levels. This study aims to find other drugs that can fix muscle cell damage without causing problems like corticosteroids do. Based on current research, it is possible that existing medications might be able to reduce the damage to muscle cell membranes when they contract in DMD. To test this idea, this study aims to develop a new way to examine muscle damage within the lab. This method can be used to test medications that are already approved for other purposes to see if they can reduce muscle damage and help with repair. Through this research, new ways to use existing medicines can be developed that are safe for people with DMD.
2024
Lead investigator
Dr Lisa Hoffman
London Health Sciences Centre Research Inc. (Lawson Health Research Institute)
London, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $99,038
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Duchenne muscular dystrophy (DMD) affects about 30,000 boys in North America, making it the most common family-inherited disease that begins during early childhood. In people with DMD, their bodies cannot correctly make the protein dystrophin. Because of this, their muscles are easily damaged and break down. Scar tissue forms, making it harder for muscles to work. Most patients die in their mid-twenties. Currently, DMD has no cure. Most DMD research is based on replacing dystrophin to build back healthy muscles. However, when boys are diagnosed with DMD around 3-5 years old, their muscles struggle to get enough oxygen and nutrients because of their poor blood supply. This significantly impairs muscle repair and makes efforts to replace dystrophin more difficult. Few studies have focused on improving blood flow to the affected muscles. Excitingly, there is now evidence of how blood flow is changed. This study suggests blood vessels are leaky, and the protein Angiopoietin -1 (Ang-1), which normally closes blood vessels, is lower in DMD-affected muscle than usual. This finding has led to the primary goal of this project: to determine if Ang-1 can close blood vessels and improve the chances of repairing muscle in lab-grown muscle by replacing dystrophin.
2024
Lead investigator
Dr Yiu-Chia Chang
University of Western Ontario
London, ON
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:Dr Yiu-Chia Chang studied Microbiology and Immunology at McGill University. He then obtained his medical degree at University of Ottawa and matched to Western University for residency training in neurology. During his residency, he developed a keen interest in neuromuscular medicine early on and took on extra rotations in the neuromuscular clinics and EMG lab. Among different sub-specialties within the neuromuscular field, Dr Chang is particularly interested in muscle diseases. During his fellowship, he aims to expand his knowledge and skills in the management of neuromuscular diseases and electrodiagnostics, as well as to acquire expertise in muscle diseases. He also aspires to be involved in medical education, with the goal of offering well-organized curriculum in neuromuscular medicine for trainees.
2024
Lead investigator
Dr Mark Krongold
University of British Columbia
Vancouver, BC
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:Dr Mark Krongold completed a bachelor’s degree in Neuroscience at the University of Calgary and medical school at Western University. He is currently completing his neurology residency at the University of Manitoba. Through his experiences in neurology, he developed an interest in electrodiagnostics and neuromuscular medicine. He looks forward to pursuing a career filled with constant learning and the chance to have a positive impact on patient’s lives. With support from the National Clinical Fellowship in Neuromuscular Medicine & Electromyography he will join the University of British Columbia for training in the upcoming year.
2024
Lead investigator
Dr Bram De Wel
University of Calgary
Calgary, AB
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:Dr Bram De Wel obtained his medical degree and completed his residency in neurology at the University Hospital Leuven in Belgium. During his residency, he obtained a PhD in neuromuscular diseases with a focus on advanced outcome measures in spinal muscular atrophy and muscular dystrophies. Dr De Wel will complete a neuromuscular medicine and EMG fellowship at the University of Calgary.
2024
Lead investigator
Dr Cedric Happi-Mbakam
SickKids Hospital
Toronto, ON
Research/Clinical Sites & Affiliations
Budget: $40,000
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Gene targeting therapy (including gene transfer/ antisense oligonucleotides and gene editing) , In vivo models , Outcome measures for neuromuscular diseases
Grant summary:Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder arising from mutations in the DMD gene, encoding the dystrophin protein. While the most common mutations involve the deletion of single or large exons, intra-exonic insertions and deletions represent approximately 3% of DMD mutations. This study will examine genetic mutations in patient myoblasts, mouse models and in vivo investigations to design and evaluate a CRISPR-Cas9 nuclease. The most efficient design will be selected and tested on a humanized mouse model. This research serves as proof of concept, and it holds promise to be adapted for other hereditary diseases sharing similar mutational profiles.
2024
Lead investigator
Dr Krista Best
Laval University
Quebec City , Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay , Friedreich ataxia
Research Areas: Advance Treatment and Care
Grant summary:Wheelchairs are often provided to people with Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and myotonic dystrophy type 1 (DM1) when they are not able to walk anymore. However, giving someone a wheelchair alone does not guarantee they will use it safely or properly. Many people who use wheelchairs need help from others to get around and they can not always do the things they like to do. This can lead to isolation, stress, and reduced quality of life. In addition, poor use of a wheelchair could lead to accidents and injuries. Previous research has recently showed that people with ARSACS have lower wheelchair skills than other adults who use wheelchairs, and that teaching wheelchair skills to people with ARSACS seems to work. This study will test the program with more people with ARSACS and DM1 to see how it can improve wheelchair mobility and confidence. This study will also examine people’s expectations and experiences with wheelchair training. People who take part in this research will answer questions before and after wheelchair training, and follow-up 3 months later to explain their wheelchair use. The results of this study may improve how therapists provide training for wheelchair use, which may improve mobility, participation, and quality of life for people with ARSACS and DM1. Learning just one wheelchair skill could be life-changing. It could mean the difference between leaving the house or not, which could impact the ability to shop for groceries, see friends, or to have a job.
2024
Lead investigator
Dr Karine Choquet
Université de Sherbrooke
Sherbrooke, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Limb girdle muscular dystrophies
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Dysferlinopathies are a rare type of muscle disease that leads to wheelchair use for most patients by the time they reach 40 years old. Dysferlinopathies affect several Canadians, most notably those of Indigenous or Acadian origin. There is currently no cure for dysferlinopathies, which are caused by spelling errors in the gene DYSF. These errors are also present in the DYSF messenger RNA (mRNA), needed to produce the protein dysferlin, which is important for repair of muscle cells. Before being used to produce protein, the DYSF mRNA must go through a process called splicing to keep only some sections called exons. Treatments for other muscle diseases change splicing to exclude certain exons that contain errors. This leads to an improvement in symptoms. This strategy shows promise for the treatment of dysferlinopathies, however it is important to better understand DYSF splicing and how modifying splicing could impact the function of DYSF mRNA. This study aims to study how DYSF mRNA is spliced, where it is located, and how much exists in healthy muscle cells. New technology that allows to read each copy of DYSF mRNA from start to finish will be used. Then, how the location and levels of DYSF mRNA change when its splicing is modified will be examined which will allow for finding which errors in DYSF can be targeted by modifying splicing. This could lead to new treatments that would improve the lives of those affected by dysferlinopathies.
2024
Lead investigator
Dr Haim Abenhaim
Sir Mortimer B. Davis - Jewish General Hospital
Montreal , Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $92,944
Disorders: All Neuromuscular Disorders (cross-cutting)
Research Areas: Advance Treatment and Care
Grant summary:This study aims to understand whether women with muscular dystrophy (MD) encounter problems if they undergo a C-section. The goal is to find the safest way for these women to have babies while reducing the chances of complications for both the mom and the baby.
There are three main questions this study aims to answer: First, do C-sections cause more issues for women with MD compared to vaginal births? Second, do these issues change based on factors like obesity or race when women with MD have C-sections? Third, is it safe for women with MD to attempt vaginal births after they had a previous C-section? To find answers to these questions, the study will use data from the 1999-2020 National Inpatient Sample in the United States. The study will use a Cohort Study consisting of women with MD who gave birth during that time and then determine the issues linked with C-sections.
The study will address challenges faced by pregnant women with MD. By providing insights, the results of this study can help doctors and women with MD make better decisions about childbirth. Ultimately, this study has the potential to improve the well-being and safety of mothers with MD and the health of their newborns.
2024
Lead investigator
Dr Rashmi Kothary
Ottawa Hospital Research Institute
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Spinal muscular atrophy (5q-SMN)
Research Areas: Discover Novel Treatments & Therapies
Grant summary:This study aims to discover a new way to treat spinal muscular atrophy (SMA) in babies before they are born. At the moment, treatment is given to babies after they are born, but this study aims to determine whether the treatment works better if given to the baby while the mother is still pregnant. This study will use mice with SMA to see if giving the treatment to the mother can stop the disease from causing problems in the baby. The results of this study have the potential to If this research works, it could mean that treating the mother with before the baby is born might be a new and better way to treat SMA patients.
2024
Lead investigator
Dr Gerald Pfeffer
University of Calgary
Calgary, Alberta
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Immune-Mediated Myopathies (Myositis) , Genetic myopathies , Limb girdle muscular dystrophies
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary:Adult onset myopathies are a group of conditions which are exceedingly difficult to diagnose despite the availability of genetic testing. The majority of cases do not obtain a genetic diagnosis, and other investigations such as muscle biopsy or MRI may not be specific enough to help diagnosis in many cases. Current research has worked on new tools for this. This study will conduct sequencing of RNA from single muscle cells using a new method developed by the research team. This will compare patients with muscle weakness to those with normal muscle. The results of this study will highlight differences in the cell proportions between groups which in turn will help people get a diagnosis for muscle disease in the future.
2024
Lead investigator
Dr Nathalie Bier
University of Montreal
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $98,697.85
Disorders: Myotonic Dystrophy
Research Areas: Amplify Research & Accelerate Knowledge , Advance Treatment and Care
Grant summary:Myotonic dystrophy type 1 (DM1) is a rare health condition that affects muscles and other body systems. It is more common in the province of Quebec. This condition can make muscles weaker over time, and it can be though for people with DM1 to do daily activities, like cooking or managing money. When discussing DM1, muscles are usually the main focus but there are also “invisible” problems, like forgetfulness and not feeling motivated, also known as cognitive problems. There is limited research on how these cognitive problems affect the lives of people with DM1, their families, and healthcare providers. This project aims to understand how cognitive problems impact daily life by using different research approaches like observing how people with DM1 do everyday tasks, completing interviews with participants, their caregivers and healthcare providers. Through these research approaches, the results of this study will identify the most important cognitive problems and how they impact certain activities. The results of this study has the potential to improve services and guide future treatments for cognitive problems among people diagnosed with DM1.
2024
Lead investigator
Dr Yassine Ouhaddi
Centre de recherche du CHU Sainte-Justine
Montreal, QC
Research/Clinical Sites & Affiliations
Budget: $40,000
Disorders: All Neuromuscular Disorders (cross-cutting) , Duchenne/Becker Muscular Dystrophy , Genetic myopathies
Research Areas: Cell-based modeling and screening , Diagnostic tools , Tissue bioengineering
Grant summary:Skeletal muscles are essential to many physiological functions; yet, because myopathies are rare and heterogeneous, diagnosing and treating them can be quite difficult. This project presents an innovative approach to advance the understanding of satellite cell-opathies, a unique group of illnesses that affect the function of muscle stem cells. This project will use muscle cells and 3D tissue engineering to test the effect of rare genetic variations linked to satellite cell-opathies on myogenic cell function. This project aims to provide insight into the molecular pathways underlying these disorders and pinpoint possible targets for treatment. This project not only lays the groundwork for investigating secondary satellite cell-opathies, which will advance our understanding of the role of muscle stem cells in disease progression, but it also holds potential for offering patients with satellite cell-opathies individualized therapy options.
2024
Lead investigator
Dr Rageen Rajendram
Holland Bloorview Kids Rehabilitation Hospital
Toronto, Canada
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $99,891.29
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Understand Diagnosis and Disorder Progression , Advance Treatment and Care
Grant summary:This study focuses on Duchenne Muscular Dystrophy (DMD), a serious muscle disorder. People with DMD eventually need help to breathe, and currently, doctors decide when to start this help based on symptoms and sleep tests, which can be slow. This study aims to change this by using artificial intelligence (AI) to predict when patients will need breathing support. This early warning can lead to better care and improved health. The AI tool developed for this study can also be used for other similar disorders. By using this new approach, this study can help doctors manage breathing problems in muscle disorders more efficiently. The findings from this study also have the potential to lead to new ways to treat and manage these disorders. In short, this study is creating a new way to help people with DMD, which could also help many others with similar health issues.
2023
Lead investigator
Dr. Francesco Saverio Tedesco
University College London
London, United Kingdom
Research/Clinical Sites & Affiliations
Funding partners: Muscular Dystrophy Canada , Cure CMD
Budget: $65,000 USD
Disorders: Collagen 6-related dystrophy (Bethlem and Ullrich congenital muscular dystrophies)
Research Areas: Discover Novel Treatments & Therapies
Grant summary:How changes in Col6 gene lead to the various symptoms seen in Col6-RD is still a poorly understood which limits amongst others clinical trial development and identification of potential drug targets. This study will develop 3D muscles created from patient-derived iPSC- myogenic and fibrogenic cells, a critical step to further understanding this disorder as well as establishing genetically relevant models to test future COL6-RD therapies.
2023
Lead investigator
Dr Eric Voorn
Amsterdam UMC, University of Amsterdam
Amsterdam, Netherlands
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Oculopharyngeal muscular dystrophy
Research Areas: Enhance Care
Grant summary:People with muscle disorders often ask advice on exercise. There is evidence for positive effects of exercise and that it is safe. Most of the studies were done in the hospital or rehabilitation center. This has some clear disadvantages. Travelling to and from the center is tiring for many people with muscle disorders. It also leads to high health care costs. An exercise program in the home environment may be a solution. There is however a lack of home-based programs for people with muscle disorders. Our team developed such an exercise program, called B-FIT in the Netherlands. B-FIT supports health care professionals to tailor the program to the patient. It can also be used to take exercise away from the hospital into the home or community. B-FIT was proven to be successful in the Netherlands. Now many health care professionals are using it there. The use of B-FIT may also be helpful for people living with muscle disorders in Canada. In this project, 20 persons with the muscle disorder called oculopharyngeal muscular dystrophy (OPMD) living in Quebec will follow the B-FIT exercise program. They will train in their own home. The program will be supervised by a trained physiotherapist. After the program, we will ask patients and therapists if they were satisfied with the use of the training guide. We will also evaluate physical fitness. We expect that physical fitness will be improved after the exercise program. This will help people with OPMD to maintain their independency and to improve their quality of life.
2023
Lead investigator
Dr Gloria Mak
University of Alberta
Edmonton, AB
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:About Dr Mak: Dr Mak completed obtained her doctor of philosophy and medical degrees from the University of Calgary and will be completing her Adult Neurology residency training at McMaster University. During residency, Dr Mak was involved in a number of patient safety and clinicopathological initiatives. She has a keen interest in the diversity and complexity of neuromuscular medicine. Dr Mak is excited to undertake fellowship training in neuromuscular medicine, as it will cultivate her skills in neuromuscular medicine, and allow her to be involved in research initiatives aimed at advancing the care of patients with neuromuscular diseases.
2023
Lead investigator
Dr Béatrice Soucy
University of Calgary
Calgary, AB
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:About Dr Soucy: Dr Soucy completed her Physical Medicine and Rehabilitation residency at Université de Montréal. She has a long-standing interest in working with patients with neuromuscular diseases as well as in medical education and physician wellness. During her training in Calgary, she will develop her expertise in management of these complex populations along with her proficiency in electrodiagnostics and ultrasound. She is thankful for the fantastic opportunity to that this clinical fellowship funding will offer her. Outside of medicine, she enjoys spending time (and sharing food) with loved ones, baking, embroidery, hiking, traveling, and taking care of her plants. Dr Soucy looks forward to coming back to Montreal after her fellowship to further develop adult neuromuscular rehabilitation in her area and ensure her future patients will receive the full scope of quality care they deserve.
2023
Lead investigator
Dr Neha Patel
University of Toronto
Toronto, ON
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:About Dr. Patel: Dr. Neha Patel is in her final year of Neurology residency training at the University of Toronto. She will be starting her Neuromuscular Medicine Fellowship in July 2023 at Sunnybrook Health Sciences Centre with Dr. Lorne Zinman and Dr. Agessandro Abrahao. She has always had an avid interest in Neuromuscular Medicine and over the last 9 years has participated in clinical, basic sciences and electrophysiologic research in myasthenia gravis, Pompe Disease and amyotrophic lateral sclerosis respectively. She hopes to continue to enhance and refine her clinical approach to Neuromuscular Medicine throughout her fellowship training, and also participate in amyotrophic lateral sclerosis research, a devastating condition which currently lacks disease-modifying treatments. Outside of work she is an avid marathon runner, scuba diver and enjoys exploring new restaurants and cuisines.
2023
Lead investigator
Sean Ng, (PhD candidate)
McMaster University
Hamilton, ON
Research/Clinical Sites & Affiliations
Budget: $40,000
Disorders: Myotonic Dystrophy
Research Areas: Understand Diagnosis and Disorder Progression , Discover Novel Treatments & Therapies
Grant summary:Grant Summary: Myotonic dystrophy is a neuromuscular condition that makes muscles very weak and unhealthy. There are two types of Myotonic dystrophy, sometimes called ‘DM’-Type DM1 and Type DM2. DM1 and DM2 have similar problems – poor muscle health. Poor muscle health in this condition may be caused by poor muscle cells. Muscle cells come from special cells called ‘stem cells’. Finding out ways to improve muscle stem cell function will help improve muscle health. It has been shown that exercise can improve DM1 muscle by activating stem cells. However, the researcher does not know if these findings also apply to DM2 muscle. This work will examine the effects of the DM2 on muscle. They will test if interventions that are beneficial for DM1 muscle can be applied to DM2 muscle. They believe that this funded work will help further understand the DM2 disease and identify ways to manage DM2.
2023
Lead investigator
Dr Tyler Churchward-Venne
The Royal Institution for the Advancement of Learning/McGill University
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Facioscapulohumeral muscular dystrophy , Muscular Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Food contains protein, which plays an important role in maintaining muscle size and function, and support overall health. Insufficient dietary protein intake can reduce muscle size and function, and impair health. How much protein should be eaten by people who have muscular dystrophy is not known. In this study, adults with muscular dystrophy will be asked to consume different amounts of protein, from very small to very large, in order to determine the optimal protein intake. We will also collect breath and urine samples to answer our research question. This study will allow us to determine how much protein people with muscular dystrophy need to consume to give their body what it needs. Eating enough protein may help people with muscular dystrophy better maintain the size and strength of their muscles and improve their quality of life.
2023
Lead investigator
Dr Reshma Amin
The Hospital for Sick Children
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $50,000
Disorders: All Neuromuscular Disorders (cross-cutting)
Research Areas: Enhance Care , Amplify Research & Accelerate Knowledge
Grant summary:Children with disorders that affect their muscles and nerves typically also have trouble with breathing. These disorders are called neuromuscular diseases (NMD). Some children with NMDs use machines to help with breathing and with coughing. These machines have been shown to improve quality of life and survival in these children, but may also be disruptive and hard to use. Most guidelines on the lung health of children with these disorders are based on what experts think because there is not enough research in this field. Recently, there have been new medicines for some of the NMDs. With all these changes to the care of children with NMD it is very important to prioritize the top research questions for scientists to focus on. This study will ask patients and families and clinicians about the questions they have about the lung health. The study has three phases. The first phase is a survey that collects research questions that are important. The second phase is a survey that narrows the research questions down to a short list. In the third phase, everybody comes together to decide on a list of the top ten research questions. This list will let people know about the most questions related to lung health for children with these neuromuscular disorders.
2023
Lead investigator
Dr Martine Tétreault
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Genetic myopathies
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary:Genes contain all of the information necessary to produce a protein. Changes in the spelling of genes can heavily change protein functions and might cause health problems. Rare neuro/muscle disorders are caused by changes in the spelling of genes important for keeping muscles healthy. With the advance of technology, we are able to diagnosis patients by identifying differences in their genetic code. We and others have shown new variants (or genetic code differences) in the gene MLIP (Muscular LMNA-Interacting Protein), thought to be liked to muscle related disorders (myopathies). Little is known yet about MLIP’s function, except that is highly expressed within the muscle. It interacts with the lamin protein, also known to be important for heart and muscles functions. We believe the altered protein is associated with a myopathy seen in children and adult patients. MLIP has only recently been linked with myopathies. Unfortunately, we do not know enough of MLIP role. As so, we will study the effect of MLIP mutations in our laboratory. More specifically, we will reproduce genetic changes found in existing patient’s genes in a cellular model. This will allow us to see how muscles are formed, maintained and affected by MLIP. We believe the study of this mutation will greatly improve our understanding of myopathies. It will also improve patient diagnosis. It will contribute to a better understanding of the role of MLIP in certain myopathies.
2023
Lead investigator
Dr. Jeanette Erdmann
University of Lübeck
Lübeck, Germany
Research/Clinical Sites & Affiliations
Funding partners: Muscular Dystrophy Canada , Cure CMD
Budget: $80,000 USD
Disorders: Collagen 6-related dystrophy (Bethlem and Ullrich congenital muscular dystrophies)
Research Areas: Discover Novel Treatments & Therapies
Grant summary:In recent years, there has been rapid development of gene therapy tools in genetic disorders. With this project the researchers are taking the first of many steps towards establishing a potential therapy using the novel CRISPRoff technology to target dominant glycine changes causing COL6-RD.
2023
Lead investigator
Dr Simon Girard
Université du Québec à Chicoutimi
Chicoutimi, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $99,600
Disorders: Myotonic Dystrophy
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary:Myotonic dystrophy type 1 (DM1) is a disorder that occurs more frequently in some regions. It is caused by the expansion of a repeated genetic sequence in the DMPK gene. However, the link between this gene and the severity of the disorder is unclear. Other genetic changes such as modifier genes have been proposed to better explain the disorder. Modifier genes affect the expression of other (main) genes. Nevertheless, few human studies confirmed the presence of such genes in patients with DM1. Here we propose to look for modifier genes in DM1 patients from the Saguenay-Lac-Saint-Jean (SLSJ). The SLSJ region has the highest incidence of DM1 worldwide, with a frequency of ~1/630, due to its strong founder effect. For this study, we will join many types of data for 200 patients with DM1 from the SLSJ. Since patients with DM1 in SLSJ mostly come from only one ancestor, we expect to see shared regions around the disorder genes. Thus, we propose to apply statistical methods to identify new modifier genes linked to DM1 in these patients. This could be the first step in beginning therapies or treatments for patients with DM1. Additionally, finding modifier genes associated with earlier DM1 onset could lead to early preventive therapies. These new findings will have an impact on DM1 research, but also for many other rare neuromuscular disorders.
2023
Lead investigator
Dr Hernan Dario Gonorazky
The Hospital for Sick Children
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: All Neuromuscular Disorders (cross-cutting)
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary:Neuromuscular disorders (NMD) can be difficult diagnoses for the most skilled clinician. Multiple approaches may be needed to achieve a final accurate diagnosis. Muscle MRI is a diagnostic tool used more often. However, it requires a high degree of expertise, which limits its use only to highly specialized centers. We propose to use artificial intelligence (AI) and machine learning (ML) to create a user-friendly mobile application. It will be able to do image segmentation, scoring, and pattern recognition. It will help to understand differences between probable diagnoses and insight of genetic results. We will work with MRI databases and key AI and ML experts from the University of Toronto. Our earlier work established the use of AI using manual scoring. It allowed the diagnosis of 10 disorders using MRI. We aim to expand our current database to 7 more childhood NMDs. If successful, we will simplify the use of muscle MRI as a diagnostic tool.
2023
Lead investigator
Dr Pascal Chartrand
University of Montreal
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Myotonic Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary:There is currently no cure for patients with myotonic dystrophy. This muscle disorder is caused by an expansion in a section of the gene – a highly repetitive sequence called CTG triplet repeats. When that happens, it can be toxic in muscles and result in defects in the alternative splicing of several transcripts. There is a great need for a drug that targets the expression of the mutant gene or its toxic product in the muscles of patients. We developed a new drug that inhibits the expression of the mutant gene. This drug corrects the mis-splicing of key transcripts in muscle cells from patients. What we want to explore in this proposal is the capacity of the drug to work in an animal model of the disorder. We will assess the activity of these drugs in a mouse model expressing a human copy of the mutant gene. We will measure how this drug reduces the expression of the toxic transcript. This project might lead to the development of new drugs for the treatment of patients with myotonic dystrophy and improve their quality of life.
2023
Lead investigator
Dr Jill Glennis Zwicker
University of British Columbia
Vancouver, British Columbia
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $83,166
Disorders: Spinal muscular atrophy (5q-SMN)
Research Areas: Enhance Care , Amplify Research & Accelerate Knowledge
Grant summary:Spinal muscular atrophy (SMA) causes severe weakness of all muscles. Until recently, it was one of the most common genetic causes of infant death. With new medical treatments, children with SMA now live, but with disabilities. Rehabilitation has always been important in the care of children with SMA. In the past, therapists used to give special equipment to children and families. Now that children with SMA can improve, rehabilitation can change to build skills. However, we don’t know what techniques are best, or what parents and children would like from therapy. Further, parents and children don’t always agree on what it is like to live with a disability or what is important to them. In this research, we will talk to people over Zoom, including parents, children and young adults with SMA, and therapists. To be youth friendly, we will invite everyone to use fun ways, such as making art and online drawings, to “create” a picture of what rehabilitation can look like. We will write out everything people say and look for patterns about what is important from different views. From what people say, the research team and patient partners will make a scheme that describes how to make rehabilitation plans for children with SMA. Our research will help make better rehabilitation plans for children with SMA. It may also help guide therapists when new medical treatments change what is possible for other conditions.
2023
Lead investigator
Dr Matthew Triolo
University of Ottawa
Ottawa, ON
Research/Clinical Sites & Affiliations
Budget: $40,000
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Understand Diagnosis and Disorder Progression , Discover Novel Treatments & Therapies
Grant summary:Grant Summary: Roughly 4 million Canadians are affected by muscular dystrophies such as Duchene Muscular Dystrophy (DMD). This disorder leads to a decline in mobility and voluntary activity. Ultimately, this results in high rates of mortality. Muscle wasting is commonly thought to be only a problem of the muscle itself. Yet, muscle stem cell (MuSC) dysfunction also plays an important role. Normally these specialized MuSC allow muscle to heal and repair itself. In patients with DMD, these cells do not work properly leading to muscle breakdown. The researchers’ recent work has shown that mitochondria are required for proper MuSC function. Unfortunately, mitochondria in MuSCs do not act well in DMD. The goal of this study is to assess whether mitochondria in MuSCs can act as a therapeutic target to treat DMD. Findings from this work will allow the researchers to target MuSCs as an intervention for DMD and other neuromuscular disorders.
2023
Lead investigator
Dr Yuguo Liu
Université de Sherbrooke
Sherbrooke, QC
Research/Clinical Sites & Affiliations
Budget: $40,000
Disorders: Duchenne/Becker Muscular Dystrophy , Collagen VI-related dystrophy (Bethlem-Ullrich) , Congenital Muscular Dystrophies , Congenital muscular dystrophy Lama2-related
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Grant Summary: Muscular dystrophies (MDs) are a group of rare muscle conditions that can affect, amongst others, young children. To date, no effective treatment is available for MD. The causes of different forms of MD are highly diverse, which makes it difficult to develop treatments that can be used for all patients. In mouse models of three different types of MD (Duchenne, Collagen 6 related, and Lama2-related muscular dystrophies), the researchers discovered that the ability of muscle to repair itself is strongly reduced. They observed that, compared to healthy muscles, this is due to a lower amount of blood flow in the tissue. They next identified a drug that is able to increase the amount of blood vessels in muscles of mouse models of MD. In all three models, this treatment led to dramatically improved self-repair of muscles. Interestingly, they found that this was due to better function of muscle stem cells. Dystrophic mice treated with this drug showed many improvements, lived longer, and became 2-3 times stronger than animals that did not receive the medication. Based on their initial discovery, they now will search for drugs that are even more effective and have a stronger treatment effect. They will also try to better understand the mechanism of action that leads to the striking reduction in disease severity. The study will lay the groundwork for a much-needed novel and highly efficient drug that can be used to treat many different forms of MD.
2023
Lead investigator
Dr James Dowling
The Hospital for Sick Children
Toronto, Ontario
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Congenital Mopathies , Centronuclear myopathy
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Centronuclear myopathy (CNM) is a common genetic form of childhood muscle disorders. Patients with CNM usually start experiencing symptoms starting from birth. The disorder can be extremely severe. It may require breathing and feeding tube support in some individuals, and can result in early death. Genetic changes in 5 different genes can cause CNM. Despite the fact that these are severe and life limiting disorders, there are no treatments. Our study will focus on one subtype of CNM caused by genetic changes in the DNM2 gene. DNM2-CNM is the second most common form of CNM. There are currently no therapies in development for DNM-CNM. We have identified several potential candidate treatments. These drugs have yet to be tested and validated in a suitable model of the disorder. The goal of this proposal is ultimately to bring treatments to patients with DNM2-CNM. We will accomplish this goal by testing promising candidate drugs in a recently developed mouse model of DNM2-CNM. Successful completion of our study will result in the first potential therapies for DNM2-CNM. The drugs we plan to test are all already Health Canada-approved. They thus hold great potential for direct translation to patients. Importantly, we have successfully used this strategy before for a different muscle disorder. This lends confidence that our approach will work for DNM2-CNM as well.
2022
Lead investigator
Dr. Thomas Durcan
McGill University
Montreal, Québec
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Myasthenia Gravis , Spinal Muscular Atrophy , Spinobulbar Muscular Atrophy , Congenital myasthenic syndromes , Lambert-Eaton Syndrome
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Motor neurons connect with muscles and control their movement through structure called neuromuscular junctions (NMJs). If motor neurons, muscles or NMJs don’t work properly, this can lead to a disorders known as neuromuscular disorders (NMDs). Most NMDs lack effective treatments. Animal models usually fail to copy human disorder making drug discovery challenging. Therefore, more relevant models are needed to study NMDs.
Our research will use human blood samples to generate stem cells. Stem cells are able to give rise to all the cell types found in the human body, including motor neurons. We have successfully cultured the motor neurons with human muscle in a dish to generate human models of the NMJ and now will use this NMJ model with different types of NMDs.
We believe that our model can be used to screen new drugs to find beneficial compounds with the potential to be advanced into clinical trials across different NMDs
2022
Lead investigator
Dr. Collin Luk
University of Calgary
Calgary, Alberta
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:Collin completed his neurology residency at the University of Alberta, where he is currently completing an ALS Clinical Research Fellowship. His research focuses on understanding the intersection of advanced neuroimaging, neuropathology and the development of biomarkers in ALS.
With support from the National Clinical Fellowship in Neuromuscular Medicine & Electromyography, he will join the University of Calgary in the upcoming year for training in EMG and neuromuscular medicine. This fellowship training will be a crucial component in his career development to becoming a clinician-scientist.
2022
Lead investigator
Dr. Alasdair Rathbone
University Hospital, London Health Sciences Centre
London, Ontario
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:Alasdair was born and raised in Hamilton, Ontario. He attended McMaster University to study Kinesiology followed by Western University in London, Ontario for his medical degree. He is currently completing his Physical Medicine and Rehabilitation residency at Queen’s University in Kingston, Ontario.
He has been interested in electrodiagnostics, neuromuscular medicine and pain management since early in his training. In residency, he has developed skills in interventional pain management and electrodiagnostics. He is excited to undertake fellowship training to improve his skills in neuromuscular medicine. His research interests have focused on myofascial pain syndrome and quantitative EMG.
Outside of work he is passionate about music (as a long time saxophone player), plants (he has over 100), playing hockey, history and spending time with his wonderful partner. He hopes to return eventually to Kingston to practice.
2022
Lead investigator
Dr. Marianne Nury
University Hospital, London Health Sciences Centre
London, Ontario
Research/Clinical Sites & Affiliations
Budget: $80,000
Disorders: All Neuromuscular Disorders
Grant summary:Marianne obtained her medical degree from Université Laval. She then chose to specialize in physiatry at Université Laval. Throughout the program, she was actively involved in extra-curricular activities and improving the curriculum. She also participated in many research projects, notably with patients with spinal muscular atrophy.
Marianne also has experience with the practice of physiatrists in Fredericton and Victoria, where she discovered and developed her keen interest in neuromuscular diseases, since it aligned with her goal of improving patient’s quality of life.
2022
Lead investigator
Dr. Emanuela Pannia
Research Institute, Hospital for Sick Children
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $40,000
Disorders: X-linked myotubular myopathy , Centronuclear myopathy , Congenital Mopathies
Grant summary:The goal of this study is to identify the cause of liver disease in X-linked myotubular myopathy (XLMTM) and the effects of diet and the immune system on its development. This study will be the first to identify causes of liver disease in XLMTM and discover new therapies to help children with this devastating disease.
2022
Lead investigator
Dr. Bernard Jasmin
University of Ottawa
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Myotonic Dystrophy
Research Areas: Understand Diagnosis and Disorder Progression , Discover Novel Treatments & Therapies
Grant summary:Myotonic Dystrophy type 1 (DM1) is a disorder affecting many organs of the body. There is currently no cure or effective treatment for the disorder. In DM1, muscles are weaker, painful and have difficulties to relax. On the molecular level multiple signaling pathways have been reported to be altered including the AMPK signaling, which is important for energy in cells. In our recent work, we found that in cell models of DM1, AMPK signaling is repressed and when it is stimulated, it improves the pathology of these cells. AMPK can be stimulated pharmacologically and physiological (i.e. through exercise.) However, it remains unknown if there is any therapeutic benefit for persons living with DM1.
In this study, we therefore propose to take our findings from cell models to further investigate the role of AMPK in persons living with DM1 and test whether endurance training has the same beneficial effects on AMPK signaling. In addition, while exercise has been shown to be beneficial for DM1 mouse models and for DM1 patients, the impact of training programs on the disorder has not been assessed.
This study will help us better understanding myotonic dystrophy, the role of exercise in muscle health and shed light on potential targets that can be developed as novel therapies for DM1.
2022
Lead investigator
Dr. Kerri Schellenberg
The University of Saskatchewan
Saskatoon, Saskatchewan
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $50,000
Disorders: Spinobulbar Muscular Atrophy
Research Areas: Enhance Care
Grant summary:Spinal bulbar muscular atrophy (SBMA; Kennedy disease) is a genetic disorder. It causes weakness, and difficulty with speaking, swallowing and breathing. Recently, we found a very high prevalence of SBMA in Indigenous people in Saskatchewan. Indigenous people affected by SBMA have told us of their wishes for more research. We have identified an approach called “photovoice” as a way to show the lived experience of people with SBMA. Pictures are used to show their lived experience. They then join group discussion with researchers. No studies to date have used the photovoice method in SBMA.
Our team’s approach adapts photovoice to Indigenous methods. We will explore the findings from photovoice using sharing circles. This study will give voice to a community that has not previously been heard. It will increase awareness about SBMA in Indigenous communities. This will hopefully help SBMA patients get access to the resources they need.
2022
Lead investigator
Dr. Craig Campbell
Western University
London, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $50,000
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary:At present there are no approved treatments for Duchenne muscular dystrophy (DMD) in Canada. One current gap is that we do not have effective and sensitive tools in place to evaluate new therapies to see if they do in fact improve health.
Our research aims at understanding if an epigenetic profile of DMD would be a potential biomarker of the muscle damage that can measure how severe the disorder is, its progression over time and if we can potentially use in the testing of new treatments. To do this we will screen blood from children impacted by DMD of different stages to see if epigenetic signatures are unique to DMD and if they change over time.
In addition to identifying potential marker for evaluating new therapies, the findings from this study could result in a faster, less expensive diagnostic screening test for DMD, and would be useful in scenarios of diagnostic uncertainty for disorders impacting the DMD gene (dystrophinopathies) like Duchenne and Becker muscular dystrophy.
2022
Lead investigator
Dr. Michael Berger
University of British Columbia
Vancouver, British Columbia
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Chronic Inflammatory demylinating polyneuropathy
Research Areas: Enhance Care
Grant summary:Chronic inflammatory demyelinating polyneuropathy (CIDP) is a condition whereby the body’s own immune system mounts an attack against the nerves in the arms and legs. This causes muscle weakness, loss of sensation and pain. One of the biggest challenges facing people with CIDP is loss of balance, which can lead to an increased risk of falls. In fact, people with CIDP report that loss of balance is the symptom they would most like to cure, of all the possible symptoms of CIDP.
Our project will address three main questions about balance in CIDP: 1) What are the causes of balance problems in CIDP?; 2) When a person is treated for CIDP, does it improve their balance?; 3) Can we measure balance in a way that is easy and quick for people with CIDP? In order to answer these questions, we will use a combination of special, highly detailed balance tests that have rarely been used for people with CIDP. We will also test whether patients’ balance is different before and after treatment. Finally, we will test whether the results from our specialized balance tests can be measured using simpler tests at the bedside.
The results of our project will promote the study of balance in CIDP. By improving knowledge about the causes of balance problems, we can design better treatments. After this study we will also be able to use balance as a tool to measure the response to different treatments for CIDP.
2022
Lead investigator
Dr. Christopher Perry
York University
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Steroid drugs and creatine are used for muscle weakness in people living with Duchenne muscular dystrophy. Steroid drugs can also cause problems with weakening mitochondria, which are the energy producing parts of muscle cells. Duchenne also makes it harder for mitochondria to use creatine for energy. This means that both treatments may not be doing the best job possible if they are also weakening mitochondria.
We discovered that two specific drugs can offset the poor metabolism that may prevent steroid drugs and creatine from helping people as much as possible. This means that these new drugs might help the other drugs work better in people with Duchenne. This study will determine if these new drugs help muscle cells from people with Duchenne produce more energy. We will also test these drugs in mice with this disorder.
We believe the results of this study will help create new drugs that will improve current treatments. If true, this could mean that people with Duchenne will have a better quality of life.
2022
Lead investigator
Dr. Maryam Oskoui
The Research Institute of the McGill University Health Centre
Montreal, Québec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Spinal Muscular Atrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary:Spinal muscular atrophy (SMA) is a rare disorder that causes muscle weakness. It is caused by low levels of a protein called survival motor neuron (SMN). Treatments that boost SMN protein make a big difference to people if started soon after they are born. For everyone else who gets treated after their muscles became weak, we need to find more ways to help them get stronger. Not much is known about how the brain is wired in SMA. The brain’s wiring depends on our movements when we are very young. Since most people with SMA become weak at a young age, their brain is probably wired differently. In other disorders, we have effective ways to help people learn and get stronger if their brain wiring is different.
In this study, we will look at the brain wiring of kids and adults with SMA and compare it with that of people without SMA to see if they are different. We will take a series of specialized brain pictures in a single session and analyze them. We will also get information about them from their medical chart such as their age and level of ability. The pictures will look both at how the brain looks and how the brain is wired. We will take the pictures exactly the same way in people with SMA as we already did for people without SMA, so we can compare them. If people with SMA have a difference in their brain wiring, it will open the door another ways of helping them reach their best potential.
2022
Lead investigator
Dr. Jodi Warman-Chardon
Ottawa Hospital Research Institute
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Oculopharyngeal muscular dystrophy
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary:Oculopharyngeal muscular dystrophy (OPMD) is a muscle disease and causes swallowing problems with face and limb weakness. OPMD is one of the most common muscular dystrophies in Canada. With new medications being tested, better methods are needed to assess how OPMD worsens or may improve with treatment. Standard MRI of the muscle can show some changes in the muscle and help with diagnosis. However, new ‘quantitative’ MRI (qMRI) can carefully assess the increasing fat in muscle as the muscular dystrophy progresses. However, qMRI has not been used to assess whole body muscle disease progression in OPMD patients.
We will use new qMRI methods to assess muscle involvement and disease progression in OPMD with whole body muscle qMRI over 1 year. We will also assess the link between qMRI and clinical weakness and strength testing. Our study will help patients with muscular dystrophy. We will study one of the largest groups with OPMD with muscle qMRI followed over time and determine if MRI predicts the disease progression. Also, this study will help guide using qMRI in future treatment trials in OPMD.
2022
Lead investigator
Dr. Rebecca Robertson
McGill University
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $40,000
Disorders: Duchenne Muscular Dystrophy
Grant summary:This project aims to fully assess issues in protein quality in DMD muscle stem cells through a variety of methods. This study will also explore how changes to CARM1 can impact the function of muscle stem cells and how they contribute to muscle repair. The ultimate goal of this work is to provide possible of treatment for DMD through these stem cells.
2022
Lead investigator
Dr. Reshma Amin
The Hospital for Sick Children
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Spinal Muscular Atrophy
Research Areas: Enhance Care , Amplify Research & Accelerate Knowledge
Grant summary:There are no programs for the transfer from pediatric to adult care for people living with Spinal Muscular Atrophy in Canada. Transition is known to be a time of worsening health due to gaps in clinical care. Therefore, this is an important area to improve upon for patients and families.
We want to learn about what it is like to be a person with SMA as they move from pediatric to adult care. We plan to do a 24-month study across 4 centers. We will talk to individuals with SMA and their caregivers who have already transitioned to adult care. We will also talk to individuals with SMA and their caregivers as they transfer to adult care at three time points: during pediatric care, after the joint transition visit and during adult care. We want to learn about the transition experience including what went well, what didn’t go well and how we can do better. We will also study the number of emergency room visits and hospital stays, quality of life, mood and stress levels during this time.
This study will be the first step towards developing specific programs across the country for people with SMA to help support them as they transfer from pediatric to adult care. What we learn can also be used to help develop programs for people with other neuromuscular disorders in Canada.
2021
Lead investigator
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
Grant summary: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.
2021
Lead investigator
Dr. Toshifumi Yokota
University of Alberta
Edmonton, Alberta
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $60,000
Disorders: Facioscapulohumeral muscular dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary: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.
2021
Lead investigator
Dr. Mohamed Chahine
Université Laval
Quebec City, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $59,987.20
Disorders: Myotonic Dystrophy
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary: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.
2021
Lead investigator
Dr. Nadine Wiper-Bergeron
University of Ottawa
Ottawa, Ontario
Budget: $60,544
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary: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.
2021
Lead investigator
Dr. Colin Crist
The Sir Mortimer B. Davis-Jewish General Hospital
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $60,000
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary: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.
2021
Lead investigator
Dr. Rima Al-Awar
Ontario Institute for Cancer Research
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $1,747,846
Disorders: Facioscapulohumeral muscular dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary: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.
2021
Lead investigator
Dr. Nicolas Dumont
Hospitalier Universitaire Sainte-Justine
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $60,000
Disorders: Myotonic Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary: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.
2020
Lead investigator
Dr. Michael Rudnicki
Ottawa Hospital Research Institute
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
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
Grant summary: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.
2020
Lead investigator
Dr. Reshma Amin
Hospital for Sick Children
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
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
Grant summary: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.
2020
Lead investigator
Dr. Rashmi Kothary
Ottawa Hospital Research Institute
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Spinal Muscular Atrophy
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary: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.
2020
Lead investigator
Dr. James Dowling
The Hospital for Sick Children
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Hereditary Myopathies
Research Areas: Discover Novel Treatments & Therapies
Grant summary: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.
2020
Lead investigator
Dr. Benjamin Gallais
Cégep de Jonquière
Jonquière, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $47,600
Disorders: Myotonic Dystrophy
Research Areas: Enhance Care
Grant summary: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.
2020
Lead investigator
Dr. Martine Tétreault
Centre Hospitalier de l’Université de Montréal
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Hereditary Myopathies
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary: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.
2020
Lead investigator
Dr. Luc Hébert
Université Laval
Quebec City, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $97,406.67
Disorders: All Neuromuscular Disorders
Research Areas: Enhance Care
Grant summary: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.
2020
Lead investigator
Dr. Hanns Lochmuller
The Children’s Hospital of Eastern Ontario
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical 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
Grant summary: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:
About the Neuromuscular Disease Network for Canada
NMD4C propelling research forward for patients, scientists and clinicians
2020
Lead investigator
Dr. Carolina Barnett Tapia
University Health Network
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $69,100
Disorders: Myasthenia Gravis
Research Areas: Enhance Care
Grant summary: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.
2020
Lead investigator
Dr. David Granville
University of British Columbia
Vancouver, British Columbia
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $100,000
Disorders: Immune-Mediated Myopathies (Myositis) , Chronic Inflammatory demylinating polyneuropathy , Myasthenia Gravis
Research Areas: Understand Diagnosis and Disorder Progression
Grant summary: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.
2020
Lead investigator
Dr. Vladimir Ljubicic
McMaster University
Hamilton, Ontario
Budget: $100,000
Disorders: Duchenne/Becker Muscular Dystrophy , Myotonic Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary: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.
2020
Lead investigator
Dr. Benoit Gentil
McGill University
Montreal, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
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
Grant summary: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.
2019
Lead investigator
Dr. Cynthia Gagnon
École de réadaptation CIUSSS du Saguenay-Lac-St-Jean
Jonquière, Quebec
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $40,639.65
Disorders: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay?
Research Areas: Enhance Care
Grant summary: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.
2019
Lead investigator
Dr. Ari Breiner
Ottawa Hospital Research Institute
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $ 49,851.00
Disorders: Myasthenia Gravis
Research Areas: Enhance Care
Grant summary: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.
2019
Lead investigator
Dr. Leanne M. Ward
Children's Hospital of Eastern Ontario
Ottawa, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $49,596.00
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Enhance Care
Grant summary: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.
2019
Lead investigator
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
Grant summary: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.
2019
Lead investigator
Dr. Gerald Pfeffer
University of Calgary
Calgary, Alberta
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Budget: $47,837.98
Disorders: Hereditary Myopathies
Research Areas: Enhance Care
Grant summary: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.
2019
Lead investigator
Dr. Anthony Gramolini
University of Toronto
Toronto, Ontario
Collaborators & Co-Investigators
Research/Clinical Sites & Affiliations
Funding partners: Jesse’s Journey
Budget: $300,000
Disorders: Duchenne/Becker Muscular Dystrophy
Research Areas: Discover Novel Treatments & Therapies
Grant summary: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.
2019
Lead investigator
Dr. Cynthia Gagnon
École de réadaptation CIUSSS du Saguenay—Lac-St-Jean
Jonquière, QC
Collaborators & Co-Investigators
Budget: $46,706.00
Disorders: All Neuromuscular Disorders
Research Areas: Enhance Care
Grant summary:Individuals impacted by neuromuscular disorders require specialized care and services which are generally offered outside of the neurological/neuromuscular clinics. Our clinic is one of the largest in Canada with more than 1600 patients under active follow-up using a health management approach and the presence of a team of internationally recognized research (Interdisciplinary Research Group on Diseases neuromuscular (GRIMN). Our clinical experience and previous research have raised questions about how well patients and their families understand research including therapeutic trials and the extent of their consent to participate in certain research initiatives such as international registers.
The objectives of this pilot project are to: 1) Create an interactive waiting room in a university clinic subspecialized in neuromuscular care aimed at informing patients and their families about various topics in research; and 2) To assess the effects of using an interactive waiting room and viewing information products to increasing patient’s knowledge.
