Over the last few years, Muscular Dystrophy Canada has diversified our research programs and partnerships. Find out about the research projects we are currently funding.
International Rare Disease consortium (E-RARE)
Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other. Review all funded projects.
Results of the 2014 E-Rare competition
After a competitive scientific evaluation by peers, the E-Rare funding bodies recommended for funding 13 excellent scientific projects on innovative therapeutic approaches for rare diseases, including projects focused on Spinal Muscular Atrophy and Nemaline Myopathy.
Common Pathogenic Pathways and Therapeutics for SMA and ALS motoneuron diseases
- Muscular Dystrophy Canada, Ilsa Mae Fund, $300,000
- CIHR’s Institute of Genetics, $390,150
- Swiss National Science Foundation $292,563
Spinal muscular atrophy (SMA) is an incurable paralytic neuromuscular disorder that mainly affects children at an incidence of 1 in 6000 to 10000 births. SMA is characterized by the selective degeneration of spinal motoneurons. About 95% of SMA cases are caused by autosomal loss-of-function mutations in the SMN1 gene. Recent work has shown that SMA and amyotrophic lateral sclerosis (ALS), another devastating motoneuron pathology, share converging aberrant pathways. The motoneuron-restricted death pathway triggered by Fas and its ligand FasL, contributes to the loss of motoneurons in ALS.
Our preliminary data shows that Fas is markedly upregulated in spinal cord motoneurons of SMA mice, suggesting that Fas may also contribute to SMA pathogenesis. Additional preliminary data demonstrates that whereas Fas undeniably induces motoneuron death, it also promotes neuronal outgrowth. Therefore, the same factor may be implicated in compensatory axonal plasticity as well as in the selective loss of neurons. Here, we propose to further dissect the functional duality of Fas and investigate the contribution of the Fas pathway in SMA pathogenesis. Activation and expression profile of the Fas pathway will be assessed in Smn depleted motoneurons, in a SMA mouse model and in human SMA spinal cord. Further, gene therapy approaches will be developed to reduce Fas activity in the spinal cord and specifically target FasL to axons in SMA mice. The ultimate goal of this collaborative endeavor is to generate common therapeutic strategies for SMA and ALS, as well as for other motoneuron diseases.
Cédric Raoul (Project Coordinator)
INM, Inserm UMR105
Ottawa Hospital Research Institute, Department of Regenerative Medicine
Swiss Federal Institute of Technology, Brain Mind Institute
Fast Skeletal Troponin Activation for Restoring Muscle Strength in Mouse Models of Nemaline Myopathy: a Molecular, Cellular, Metabolic and Functional Assessment
Problem to be solved: No treatment is available for nemaline myopathy (NM), a rare and fatal muscle disease.
Background: A cardinal feature of NM is muscle weakness, caused by atrophy, impaired sarcomere contractility and alterations in energy pathways. This research program builds on our recent in vitro studies, funded by E-RARE1, which suggest that muscle strength in NM might be restored by fast skeletal troponin activation. Preclinical studies with fast skeletal troponin activators in live NM mice are now warranted.
Objective: Determine the efficacy of the fast skeletal troponin activator tirasemtiv in live NM mice.
Approach: Tirasemtiv will be tested in four NM mouse models: this allows us to cover a large spectrum of the disease. We will study its effect on muscle function, energy metabolism and NM biomarkers using non-invasive magnetic resonance imaging and spectroscopy, measurements of in vivo and ex vivo muscle strength and proteomic assessments of the involved signaling pathways. This combination allows for an in-depth analysis of the efficacy of tirasemtiv in NM mice.
Innovation: The availability of (1) four NM mouse models, (2) high-end infrastructure to assess muscle – and whole body performance, and (3) a novel and promising drug, positions us ideally to tackle the problem posed.
Impact: Our research program is positioned at the level of basic science and its translation towards direct clinical application; its outcome might provide an impetus to preclinical studies in other disorders with muscle weakness.
VU University Medical Center Laboratory for Physiology Institute for Cardiovascular Research
Amsterdam, The Netherlands
Fondazione Salvatore Maugeri
Aix Marseille University
Results of the 2013 E-Rare competition
After a competitive scientific evaluation by peers, the E-Rare funding bodies recommended for funding 12 excellent scientific projects, 6 of which have a Canadian component. The funded projects cover a wide range of rare diseases including neuromuscular disorders.
Muscular Dystrophy Canada is pleased to be contributing over $380,000 towards the 2 Canadian teams that are focused on neuromuscular research.
F. Jeffrey Dilworth
Ottawa Hospital Research Institute
Centre Européen de Recherche en Biologie et en Médecine (CERBM-IGBMC)
Despite the fact they constitute two thirds of the human genome, repetitive sequences are largely ignored. FSHD is an autosomal dominant disorder with a strong epigenetic component. Unlike the majority of genetic diseases, FSHD is not caused by mutation in a protein-coding gene. Instead, the disease is associated with a reduced copy number of the D4Z4 macrosatellite repeat mapping to 4q35. Despite years of intensive research, the molecular pathogenesis of FSHD remains largely unknown. We recently identified DBE-T, a chromatin-associated lncRNA produced preferentially in FSHD patients. DBE-T mediates a Polycomb to Trithorax epigenetic switch at the FSHD locus, driving chromatin remodeling and de-repression of 4q35 protein-coding genes in FSHD patients. In FSHD, up-regulation of multiple 4q35 candidate genes has been reported. Based on this, it has been suggested that FSHD could be considered a continuous gene disease in which the epigenetic alteration of multiple genes contributes to the final outcome. Since DBE-T behaves as a master regulator of the FSHD locus being required to activate all FSHD candidate genes, it is a very intriguing candidate to develop therapeutic approaches aimed at normalizing 4q35 gene expression in FSHD patients. Nevertheless, DBE-T mechanism of action is poorly understood. Here we propose to tackle these issues by addressing the following questions: – Is DBE-T responsible for the enhanced disease penetrance of FSHD in muscle? – How is DBE-T tethered to chromatin? – How does DBE-T activate FSHD candidate genes?
Stimulating Intrinsic Repair for DMD
Duchenne Muscular Dystrophy (DMD) is a rare and devastating genetic disease of childhood manifested by progressive debilitating skeletal muscle weakness and wasting, and ultimately death. The Rudnicki group recently identified a role for Wnt7a/Fzd7 signaling in stimulating the regeneration of muscle by acting at two levels. Wnt7a acts on satellite stem cells to drive their symmetric expansion, and also acts on myofibers to stimulate hypertrophy. Delivery of Wnt7a significantly ameliorated dystrophic changes in the mdx mouse model of DMD. The research team represents an outstanding multidisciplinary group of investigators, who are uniquely positioned to conduct the proposed basic and preclinical studies. The overall goal of the project is to assess the utility of Wnt7a and its variants as protein therapeutics for the stimulation of intrinsic regeneration for the treatment of DMD. We propose to characterize the effects of whole body treatment in mdx mice using transgenesis as well as systemic delivery of Wnt7a. We will characterize the Wnt7a/Fzd7 signaling pathway at the molecular level and identify downstream target genes to elucidate mode of action. We will investigate the basis for the suppression of the inflammatory response by Wnt7a. Finally, we will assess the activity of Wnt7a on human satellite cells and myofibers in mice carrying humanized DMD muscle. These experiments will advance our knowledge of Wnt7a signaling in muscle and illuminate the therapeutic potential of Wnt7a as a protein biologic to stimulate intrinsic repair in a muscle-wasting disease like DMD.
Respiratory Care Grants
Since 2012, Muscular Dystrophy Canada’s has focussed our services to provide information and raise awareness about the importance of respiratory health. We continue to work to ensure that people affected by neuromuscular disorders have access to the right services and care, and we will speak up and advocate for changes when challenges are identified.
Through our work in this area, we have come to understand that there is a need for investment into research to enhance the scientific evidence that is available to inform respiratory care decisions.
Under the expert guidance of our Medical and Scientific Advisory Committee, in April 2014, we launched a request for proposals for projects related to improving the respiratory health for people living with neuromuscular disorders.
The following four (4) projects were awarded funding:
- Health Service Utilization for Assessment, Monitoring and Management of Respiratory Complications for Individuals with Neuromuscular Disease ($49,690).
Principal Investigator: Louise Rose, PhD (University of Toronto)
Co-applicants: Douglas McKim (Ottawa Hospital); David Leasa (London Health Sciences Center); Mika Nomoyoma (University of Toronto); Anu Tandon (Sunnybrook); Reshma Amin (Sick Kids); Sherri Katz (CHEO); Andrea Gershon and Roger Goldstein (West Park).
- A respiratory focused e-learning resource for people living with neuromuscular diseases and their families ($47,303).
Principal Investigator: Judy King (University of Ottawa)
Co-applicants: Douglas McKim, Carole LeBlanc (The Ottawa Hospital)
- A comparison of three methods for improving expiratory cough flow and lung volume in children with neuromuscular diseases ($17,025)
Principal Investigator: Michael Seear (BC Children’s Hospital)
Co-applicants: Kathy Selby and Maggie McIIwaine
- Understanding Decision Needs for Respiratory Interventions in Pediatric Neuromuscular Disorders: Laying the Foundation for Developing a Shared Decision Environment for Respiratory Care Decisions ($49,920)
Principal Investigator: Craig Campbell (Children’s Hospital, London Health Science Centre)
Co-applicants: Margaret Lawson and Sheri Katz (CHEO); Lawrence Korngut (University of Calgary); Jean Mah (Alberta Children’s Hospital); April Price and Dhenuka Radhakrishnan (Children’s Hospital, LHSC)
Neuromuscular Research Partnership
The Neuromuscular Research Partnership supports the following research projects (listed in alphabetical order by investigator surname).
Characterization of a novel function for PABPN1: the product of the oculopharyngeal muscular dystrophy disease gene
François Bachand, PhD
Université de Sherbrooke
Dr. François Bachand
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset form of the disease that, while found worldwide, affects French Canadian and Jewish populations more frequently. Symptoms include drooping eyelids, difficulty swallowing, and limb weakness. The genetic mutation responsible for OPMD is known, but nothing is known about the underlying mechanism by which the mutation causes OPMD. Dr. Bachand and his team are investigating the function of the responsible gene, called PABPN1. Their work could address why OPMD is limited to specific muscles and open the way to new treatments.
Misfolding of Cu/Zn superoxide dismutase by pathological FUS and TDP43: relevance to ALS
Neil Cashman, PhD
University of British Columbia
Dr. Neil Cashman
While amyotrophic lateral sclerosis (ALS) can be caused by a variety of inherited gene mutations, the majority of cases occur sporadically. Dr. Cashman and his team believe that misfolding of copperzinc superoxide dismutase (SOD1), an enzyme that is an important antioxidant defense, may represent a common pathological pathway for both familial and sporadic ALS. They have already shown pathological TDP-43 and FUS are associated with SOD1 misfolding. Confirming a common molecular pathway in ALS that involves these proteins and the misfolded SOD1 will have important implications in the design of effective treatments in the future.
Differential role of myogenic regulatory factors in establishing muscle-specific gene expression
Jeffrey Dilworth, PhD
Ottawa Hospital Research Institute
Dr. Jeffrey Dilworth
Myogenin regulates gene expression and plays a critical role in deciding which genes to turn on in muscle cells. Dr. Dilworth is determining how this decision is made. His work will shed light on the developmental process that gives rise to muscle cells, including identifying cellular proteins that collaborate with myogenin. His work will contribute to the development of stem cell-based therapies for muscular dystrophy.
Rank/RankI/OPG: a new pathway that regulates skeletal muscle disuse, aging and disease
Jérôme Frenette, PhD
Dr. Jérôme Frenette
Nearly 65% of our body weight is made of bones and skeletal muscles. They control many important functions in the body, including movement, breathing, and the production of blood cells, but aging, injury, and neurodegenerative diseases can cause them to atrophy. Building on exciting advances in bone biology and disease, Dr. Frenette and his team want to bridge the physiopathology (the study of bodily disturbances caused by disease) of bones and muscles. Their early results indicate that a pathway that plays a role in bone homeostasis also features in muscle wasting and muscular diseases in some skeletal muscles, notably those essential for brief and powerful movements. Dr. Frenette and his team believe that this pathway, known as the Rank/RankL/OPG pathway, is an important actor in skeletal and possibly even cardiac diseases.
Molecular basis of ryanodine receptor regulation and function in skeletal and cardiac muscle
Anthony Gramolini, PhD
University of Toronto
Dr. Anthony Gramolini
Dr. Gramolini’s research is aimed at providing a detailed study of the mechanics of skeletal muscle function and the role played by calcium regulatory proteins in normal muscle function and skeletal muscle diseases. By understanding the ryanodine receptor (RyR) calcium release channel (which regulates the movement of calcium ions that are involved in muscle contraction and relaxation), Dr. Gramolini and his team hope to increase their knowledge of calcium release in muscle. That information could prove crucial to identifying new cellular targets for therapeutic intervention in RyR-based muscle diseases, such as central core disease and malignant hyperthermia.
Growth arrest and osteoporosis in Duchenne muscular dystrophy patients treated with glucocorticoids
Marc Grynpas, PhD
Mount Sinai Hospital, Toronto
Dr. Marc Grynpas
Children with Duchenne muscular dystrophy (DMD) are often treated with high-dose glucocorticoids, which substantially reduce mortality rates, but which also result in disordered bone health, potentially causing fractures, bone pain, and vertebral compression. While a number of factors contribute to poor bone health in children—such as nutrition, genetic factors, and growth—studies in adults are of limited use. Dr. Grynpas and his team believe that by understanding the cause of osteoporosis, growth arrest (an interruption of normal bone growth), and the signaling pathways in bone, they can develop an approach to prevent and treat disordered bone health in DMD, thereby alleviating the additional burden that it causes.
Post-transcriptional Regulation of Utrophin in Skeletal Muscle: Implications for new therapeutic strategies for Duchenne muscular dystrophy
Bernard Jasmin, PhD
University of Ottawa
Dr. Bernard Jasmin
Duchenne muscular dystrophy (DMD) is the most prevalent inherited neuromuscular disorder, but there is still no effective cure or treatment for the disease. Resulting in mutations or deletions in the X-linked (or male) dystrophin gene, DMD prevents the production of full-length dystrophin, the protein that is crucial to muscle function. One possible therapy is the use of utrophin, a protein similar to dystrophin that might compensate for the lack of the other protein. Building on his previous research on the subject, Dr. Jasmin seeks to decipher the mechanisms involved in controlling utrophin in normal and DMD muscle fibres, information that one day might form the basis for the design of pharmacological intervention that increases the expression of utrophin in DMD muscle fibres.
Magnetic resonance imaging biomarkers in ALS
Sanjay Kalra, PhD
University of Alberta
Dr. Sanjay Kalra
After decades of clinical trials, there is no therapy with a meaningful effect on survival in ALS. Despite an increasing understanding of the complex pathogenic mechanisms, an important barrier to finding treatment is the lack of a human biomarker—or indicator—of cerebral degeneration. A biomarker would play an essential role in the evaluation of novel drugs, reduce delays in diagnosis, and provide insight into the biological factors related to the variability in the effects of ALS. Using magnetic resonance imaging (MRI), Dr. Kalra and his team intend to assess different regions of the brain, which in turn will allow correlations to be made with patient behaviour. Ultimately, Dr. Kalra hopes to test the capacity of MRI biomarkers to predict the progression of the disease while validating the biomarkers at several different stages. These are essential steps towards developing successful treatments for ALS that will increase our understanding of this terrible and diverse disorder.
Folding and aggregation of ALS-associated mutant superoxide dismutases
Elizabeth Meiering, PhD
University of Waterloo
Dr. Elizabeth Meiering
ALS is the most common cause of neurological death each year in both Canada and the United States. The major known cause of ALS is mutations in a protein called superoxide dismutase (SOD). Dr. Meiering is examining whether mutations in SOD cause it to mis-fold, leading to the formation of toxic aggregates that, in turn, give rise to ALS. Her work will contribute to a better understanding of the mechanisms of ALS and help in the development of therapies for the disease.
Identifying novel roles of calcineurin signaling in the control of complementary pathways affecting the dystrophic phenotype
Robin Michel, PhD (Concordia University)
Bernard Jasmin, PhD (University of Ottawa)
Thanks to landmark studies performed by Drs. Michel and Jasmin and their teams, we know calcineurin, an enzyme that orchestrates muscle growth, has a significant effect on utrophin, a protein that can compensate for the lack of dystrophin (another protein) in dystrophic muscle fibres. Drs. Michel and Jasmin now intend to take the next logical step to further define the role of calcineurin in rescuing damaged dystrophic muscles and identify other novel players involved in this rescue. They believe these experiments will contribute to our understanding of the biochemical and molecular regulatory events that are involved in this disease, thereby providing potential therapeutic targets and strategies to reverse its damaging effects.
Artificial zinc finger transcription factors targeting the utrophin promoter as a potential therapy for Duchenne muscular dystrophy
Josephine Nalbantoglu, PhD
Dr. Josephine Nalbantoglu
One possible avenue for treating Duchenne muscular dystrophy (DMD) is to increase the activity of a protein called utrophin (which is similar to the protein that is missing in people with the disease, called dystrophin) so that utrophin becomes present throughout the surface membrane of muscle fibres, instead of its normal, very restricted, localization. Dr. Nalbantoglu and her team have already developed a protein called an artificial transcription factor in mice to increase the amount of mouse utrophin. This project will use the same approach to design artificial transcription factors that target the human utrophin gene to increase its amounts. This approach could eventually be used to treat DMD.
Strategies for therapy of respiratory muscle failure in muscular dystrophy
Basil Petrof, PhD
The Research Institute of McGill University Health Center
Dr. Basil Petrof
Affecting approximately 1 in 3500 males, Duchenne muscular dystrophy (DMD) is the most frequent disorder linked to the X chromosome. Patients often die of respiratory failure as the disease progressively destroys muscle (such as the diaphragm and other respiratory muscles) and prevents normal muscle repair. Dr. Petrof and his team want to better understand the factors that regulate muscle damage and repair in DMD in order to identify new therapeutic strategies for the disease. By examining the role of the immune system in balancing muscle damage and repair, they hope to determine whether manipulating an individual’s innate immunity could provide a way of treating respiratory muscle failure that is caused by DMD.
Development of better and more effective treatment for patients affected by hyperkalemic periodic paralysis (HyperKPP)
Jean-Marc Renaud, PhD
University of Ottawa
Dr. Jean-Marc Renaud
Characterized by periods of uncontrolled muscle contractions in the limbs, hyperkalemic periodic paralysis (HyperKPP) can leave patients confined to bed for hours or even days. While these contractions and paralysis may cease after the age of 30, patients continue to suffer muscle weakness, making walking difficult or even impossible. Currently, none of the treatments for HyperKPP are fully effective, but Dr. Renaud hopes to document the mechanism of the disease in order to develop new and more effective therapeutic approaches.
“Our ultimate objective is to find a better treatment that would eliminate the HyperKPP symptoms and this constitutes the direct benefit of our research. At the same time, there are many other neuromuscular diseases that are related to defect in ion channels. Understanding the mechanisms of HyperKPP, will indirectly help understanding the mechanism of other Chanelopathies as well as helping find better treatment.”
Therapeutic properties of the innate immune response by microglia
Serge Rivest, PhD
Dr. Serge Rivest
Microglia are the main immune cells of the central nervous system. They accumulate in degenerating regions of the brain, producing a wide variety of inflammatory molecules that may have beneficial or detrimental effects. Dr. Rivest and his team are investigating whether these cells can be activated to create a kind of natural immunotherapy that more effectively clears pathogens, cell debris, and toxic substances that are produced in chronic disease. This research could lead to the development of new strategies to help repair the injured brain and, ultimately, to find cures for brain diseases such as ALS.
Genetic Regulation of Myogenesis
Michael Rudnicki, PhD
Ottawa Hospital Research Institute
Dr. Michael Rudnicki
Appearing in early childhood, Duchenne muscular dystrophy (DMD) is a devastating inherited muscular disorder that leads to progressive and debilitating muscle weakness and wasting, ultimately resulting in death. Dr. Rudnicki proposes to investigate the basis for the altered function of muscle stem cells in DMD. He is investigating whether muscle stem cells have undergone epigenetic changes, alterations in chromosomal structure caused by the disease environment that change the expression of genes involved in regulating stem cell function.
Dr. Rudnicki believes that such insight into the factors that contribute to the cause of DMD will lead to new modes of therapeutic intervention.
Satellite stem cells from skeletal muscle for the treatment of neuromuscular disease
Michael Rudnicki, PhD
Ottawa Hospital Research Institute
Dr. Michael Rudnicki
The growth and repair of skeletal muscle in adults is linked to a group of cells called “satellite cells” that associate with muscle fibres. Dr. Rudnicki and his team have not only discovered another group within that satellite cell grouping that they have named “satellite stem cells,” but they have also identified Wnt7a, a protein that stimulates activity in those stem cells. By investigating these satellite stem cells and their interaction with Wnt7a, Dr. Rudnicki hopes to gain information about how muscle stem cell function is controlled and how those cells contribute to the regeneration of skeletal muscle. Ultimately, this knowledge could open new avenues for the treatment of diseases such as muscular dystrophy.
Regeneration of motor neurons controlling movement and respiration from embryonic stem cells
Stephano Stifani, PhD
Dr. Stephano Stifani
Recent progress in the field of regenerative medicine has highlighted the therapeutic potential of undifferentiated stem or progenitor cells in the replacement of neurons (nerve cells that are the core components of the nervous system) that have been lost as a result of injury or disease.
While this possibility is hindered by our lack of understanding of how specialized motor neurons are formed and become integrated into functional circuits—particularly those affected by motor neuron diseases like ALS—Dr. Stifani and his team want to study the mechanisms that control the development of these specific types of motor neurons. By arriving at a precise understanding of how particular motor neurons are generated and connected during development, Dr. Stifani hopes to facilitate the development of new strategies that promote motor neuron regeneration, replacing neurons that are lost or damaged by disorders such as ALS.
Regulation of motor neuron identity and circuit development
Stephano Stifani, PhD
Dr. Stephano Stifani
Motor neurons are particularly vulnerable to degeneration in diseases such as ALS, but how are they generated and formed into functional motor circuits? Despite significant advances in stem cell-based regenerative therapies, we simply don’t know, and Dr. Stifani and his team want to change that. By studying a group of hindbrain motor neurons (part of the central nervous system) known as the hypoglossal nucleus, they want to characterize how these neurons control vital functions like chewing, swallowing, and breathing. Understanding how these motor neurons are generated and form connections will facilitate strategies that promote the regeneration of motor neurons in the affected area.
Correction of the dystrophin gene with Zinc Finger Proteins and TAL effector nuclease
Jacques Tremblay, PhD
Dr. Jacques Tremblay
Dr. Tremblay intends to develop a completely new therapeutic avenue for Duchenne muscular dystrophy (DMD) by targeting specific sequences in the dystrophin gene with engineered endonuclease proteins (enzymes that cleave the DNA chain). By using these specifically engineered endonucleases, Dr. Tremblay believes that the reading frame (i.e., groups of 3 nucleotides that code for one amino acid) of the dystrophin gene can be corrected, thus restoring dystrophin expression, which is lacking in patients with DMD. The objective of the project is to inject these meganucleases—fused with a cell-penetrating peptide—into the blood of DMD patients so that the proteins can enter in the muscle fibers and potentially correct the dystrophin gene. In time, genetic corrections like this may also be eventually used to treat other neuromuscular diseases.
“My research program aims to develop a cell therapy for recessive muscular dystrophies. The cell therapy that we are trying to develop will not only permit to introduce the normal gene in the muscle fibers of patients with various recessive muscular dystrophies but will also introduce in the muscles new muscle precursor cells that will increase its regenerative capacity.”
Studies on the molecular pathogenesis of amyotrophic lateral sclerosis (ALS)
Hiroshi Tsuda, PhD
Montreal Neurological Institute
Dr. Hiroshi Tsuda
ALS is a neurodegenerative disorder caused by the progressive loss of motor neuron function in the brain and spinal cord. As a result, patients with ALS will lose the ability to stand, walk, or use their hands and arms, and will eventually suffer respiratory failure. While there is no primary therapy for ALS, Dr. Tsuda will study Drosophila, or fruit flies, in order to better understand what events at the molecular level lead to the onset of ALS. By doing so, Dr. Tsuda hopes to gain insight into ALS that could lead to a more effective treatment of the disease.
Molecular mechanisms regulating myotubularin-related 2 lipid phosphatases mutated in neuromuscular disorder Charcot-Marie-Tooth disease
Panayiotis Vacratsis, PhD
University of Windsor
Dr. Panayiotis Vacratsis
Charcot-Marie-Tooth (CMT) disease is a common group of disorders of the peripheral nervous system that is characterized by demyelination (where the myelin sheath of neurons is disrupted), resulting in the progressive decrease of muscle tissue and touch sensation across parts of the body. The gene encoding MTMR2 (part of the MTM family of enzymes) is mutated in a certain aggressive form of Charcot-Marie-Tooth disease (CMT4B). Dr. Vacratsis’ research group wants to ultimately understand why the loss of a functional MTMR2 enzyme causes CMT. Moreover, a detailed understanding of MTMR2 biology will provide the necessary framework to identify and subsequently develop novel therapeutic strategies for CMT disease.
Cell biological mechanisms of TDP-43 in ALS
Christine Vande Velde, PhD
University of Montréal
Dr. Christine Vande Velde
Nearly 3,000 Canadians live with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that attacks motor neurons, and there is no treatment that will appreciably slow or treat the disease. Efforts to design therapies are hampered by our lack of understanding of the pathogenesis of the disease (the mechanism by which it is caused), but a DNA binding protein known as TDP-43, has emerged as a player in the mutations that cause some forms of ALS. TDP-43 regulates stress response in cells through stress granules (aggregations of protein and RNA that appear when a cell is under stress), a process that is affected by disease-causing mutations, making motor neurons vulnerable. Dr. Vande Velde and her team intend to further our understanding of TDP-43 by examining how it interacts with stress granules in the hope of identifying new targets for future therapeutic development.