Halifax - Dalhousie University

Paul Liu, Ph.D.
(PPG) Gene therapy for Duchenne muscular dystrophy (DMD)
$ 100,764.00	1/1/00 - 12/31/00	Year 1
$ 107,460.00	1/1/01 - 12/31/01	Year 2
$ 106,400.00	1/1/02 - 12/31/02	Year 3

Summary: This project is to develop a method of gene therapy for DMD. It focuses on gene delivery using two new technologies: rAAV vector and protein trans-splicing.

Hamilton - McMaster University

Michael Rudnicki, Ph.D.
(RG) Molecular regulation of myogenic stem cell function
$ 60,000.00	1/1/00 - 12/31/00	Year 2
$ 60,000.00	1/1/01 - 12/31/01	Year 3

Summary: Researchers propose to investigate the molecular mechanisms that regulate muscle regeneration. Insights from this work may lead to novel modes of therapy in the treatment of muscular dystrophy.

Mark Tarnopolsky, M.D., Ph.D.
(RG) Use of creatine monohydrate in muscular dystrophy
$ 70,750.00	1/1/00 - 12/31/00	Year 1
$ 67,750.00	1/1/01 - 12/31/01	Year 2

Summary: Researchers hypothesize that creatine monohydrate supplementation will be a safe and effective treatment to increase muscle mass and strength in patients with some forms of muscular dystrophy.

Montreal - McGill University

Douglas Arnold, M.D.
(RG) Therapy for mitochondrial myopathies
$ 79,488.00	1/1/00 - 12/31/00	Year 2

Summary: Researchers will attempt a new approach to therapy for mitochondrial myopathies called "gene shifting," in which exercise is used to shift a patient's own normal mitochondrial genes into their own muscle.

Salvatore Carbonetto, Ph.D.
(RG) Studies of muscular dystrophy in dystrophin deficient mice
$ 75,000.00	1/1/00 - 12/31/00	Year 1
$ 75,000.00	1/1/01 - 12/31/01	Year 2
$ 75,000.00	1/1/02 - 12/31/02	Year 3

Summary: The studies proposed here will describe a novel animal model for dystroglycan-deficient muscular dystrophy that is relevant to many muscular dystrophies. The studies will detail pathways involved in dystroglycans and their dysfunction in muscular dystrophies.

Heather Durham, Ph.D.
(RG) Investigation of therapeutic strategies for amyotrophic 
lateral sclerosis (ALS) in a primary culture model
$ 61,145.00	1/1/00 - 12/31/00	Year 3

Summary: Using a cell culture model of familial ALS, researchers will study the reasons why motor neurons are particularly vulnerable to damage and formulate and test therapeutic strategies that may be beneficial in many motor neuron diseases.

Paul C. Holland, Ph.D.
(RG) The role of the primary adenovirus receptor 
in the efficacy of adenovirus-mediated gene transfer to muscle
$ 69,306.00	7/1/99 - 6/30/00	Year 2
$ 68,226.00	7/1/00 - 6/30/01	Year 3

Summary: Researchers will determine if the virally-mediated gene therapy of neuromuscular diseases can be made more efficient by causing muscle to make more of a protein that virus vectors use to enter mammalian cells.

George Karpati, M.D.
(RG) Molecular therapies for dystrophin deficiency
$ 73,919.00	1/1/00 - 12/31/00	Year 1
$ 75,000.00	1/1/01 - 12/31/01	Year 2
$ 75,216.00	1/1/02 - 12/31/02	Year 3

Summary: The proposed experiments are aimed at optimizing the conditions for an efficient adenovirus-mediated dystrophin gene transfer or utrophin gene upregulation in muscles of the mdx mouse model of Duchenne muscular dystrophy (DMD). In due course, the fully optimized paradigm of either of these molecular treatment strategies is expected to be tested in therapeutic trials in DMD patients.

Basil Petrof, M.D.
(RG) Adenovirus-mediated delivery of therapeutic genes 
in Duchenne muscular dystrophy (DMD)
$ 60,000.00	1/1/00 - 12/31/00	Year 2
$ 60,000.00	1/1/01 - 12/31/01	Year 3

Summary: The purpose of this proposal is to test methods for achieving widespread gene delivery and preventing harmful immune system responses to gene therapy for DMD.

Eric A. Shoubridge, Ph.D.
(RG) Assembly of cytochrome c oxidase in mitochondrial myopathy
$ 78,651.00	7/1/99 - 6/30/00	Year 1
$ 60,000.00	7/1/00 - 6/30/01	Year 2
$ 60,000.00	7/1/01 - 6/30/02	Year 3

Summary: Researchers will investigate the function of a protein that appears to be critical for the assembly of a protein in the oxidative energy producing system of muscles and nerves.

George Snipes, M.D., Ph.D.
(RG) PMP-22 related hereditary peripheral nerve diseases
$ 46,036.00	7/1/99 - 6/30/00	Year 3

Summary: Researchers will study both the effects of PMP-22 protein mutations that cause disease (CMT) in peripheral nerve and also the regulation of the PMP-22 gene.

Montreal - Montreal General Hospital Research Institute

Guy Rouleau, M.D., Ph.D.
(RG) Molecular pathophysiology of oculopharyngeal muscular dystrophy (OPMD)
$ 125,000.00	1/1/00 -12/31/00	Year 3

Summary: OPMD is a hereditary disease which mostly affects the muscles responsible for the elevation of the eyelids and swallowing. Researchers propose to study how the PAB2 gene causes the symptoms and develop animal and cellular models of OPMD to study how the disease develops and test new treatments.

(RG) Identification of new familial amyotrophic lateral sclerosis (ALS) loci
$ 60,000.00	7/1/99 - 6/30/00	Year 2
$ 60,000.00	7/1/00 - 6/30/01	Year 3

Summary: ALS is caused by premature death of brain cells resulting in weakness. While most ALS cases are sporadic, 10% are hereditary (FALS). The SOD1 gene causes 20% of FALS, researchers will look for the cause of the remaining FALS.

Montreal - University of Montreal

Massimo Pandolfo, M.D.
(RG) Molecular pathogenesis of Friedreich's ataxia (FA)
$ 80,000.00	1/1/00 - 12/31/00	Year 3

Summary: FA is an inherited disease resulting in movement incoordination and heart disease caused by the deficiency of a protein involved in iron metabolism. Researchers will investigate the function of this protein in detail and the possibility of correcting the consequences of its deficiency by drug treatment.

(EMG) Restricted funds for the support of Friedreich's ataxia research
$ 70,000.00	4/1/99 - 3/31/00	Year 2

Ottawa - Children's Hospital of East Ontario

Robert Korneluk, Ph.D.
(RG) Mouse models of myotonic dystrophy (MMD)
$ 60,000.00	7/1/99 - 6/30/00	Year 3

Summary: Research will create mouse models of MMD using a transgenic approach. With these models, study of how the mutation associated with MMD causes the disease and how instability of the mutation arises as it is passed from parent to offspring, will be possible.

Ottawa - Ottawa General Hospital

Christine DiDonato, Ph.D.
(DG) Creation of an animal model for 
spinal muscular atrophy (SMA)
$ 35,000.00	1/1/00 - 12/31/00	Year 2
$ 35,000.00	1/1/01 - 12/31/01	Year 3

Summary: Researchers will create subtle mutations within the SMN , the gene causing SMA, which will reduce the protein level and allow analysis of SMN function in vivo.

Rashmi Kothary, Ph.D.
(RG) Role of dystonin/Bpag 1, a cytoskeletal linker 
protein, in muscle integrity and myopathy
$ 60,000.00	1/1/00 - 12/31/00	Year 2
$ 60,000.00	1/1/01 - 12/31/01	Year 3

Summary: Researchers will determine how dystonin deficiency causes an instability of skeletal muscle cytoarchitecture by investigating the muscle proteins (like desmin) that normally interact with it.

Lynn A. Megeney, Ph.D.
(RG) Defining the molecular basis for 
dystrophy-associated cardiomyopathy
$ 60,000.00	1/1/00 - 12/31/00	Year 2
$ 60,000.00	1/1/01 - 12/31/01	Year 3

Summary: An animal model will be used to explore the effect that skeletal muscle damage may impose on the dystrophic heart.

Ottawa - University of Ottawa

Bernard Jasmin, Ph.D.
(RG) Regulation of utrophin gene expression in developing and adult muscle cells
$ 70,000.00	1/1/00 - 12/31/00	Year 3

Summary: An approach to counteract the effects of Duchenne muscular dystrophy (DMD) consists in utilizing a protein normally expressed in diseased muscle which could compensate for the lack of dystrophin. A good candidate for this role is utrophin. In this context, it thus becomes essential to understand how expression of utrophin is regulated.

Ste-Foy - Laval University

Jack Puymirat, M.D., Ph.D.
(RG) Evaluation of a gene therapy for myotonic dystrophy (MMD)
$ 39,779.00	1/1/00 - 12/31/00	Year 1
$ 39,779.00	1/1/01 - 12/31/01	Year 2
$ 39,217.00	1/1/02 - 12/31/02	Year 3

Summary: This proposal outlines an ordered series of experiments aimed at testing a myotonic gene therapy based on gene silencing associated with gene replacement.

Jacques Tremblay, Ph.D.
(PPG) Improving myoblast transplantation
$ 167,432.00	1/1/00 - 12/31/00	Year 3

Summary: Earlier results of myoblast transfer clinical trials demonstrated that more basic scientific studies were needed to enhance the procedure's potential as a treatment for DMD. This project is designed to improve cell transplantation methods in the laboratory with the prospect of applying the technology to increase muscle strength in those affected by DMD.

Toronto - Hospital For Sick Children

Peter Ray, Ph.D.
(RG) Identification of proteins interacting with syntrophin
$ 55,000.00	1/1/00 - 12/31/00	Year 3

Summary: The goal of this project is to identify additional members of the dystrophin-syntrophin protein complex that is required for synaptic function at the neuromuscular junction and in the CNS.

Toronto - University of Toronto

Henry Klamut, Ph.D.
(RG) Duchenne muscular dystrophy (DMD) gene regulation in muscle
$ 60,000.00	1/1/00 - 12/31/00	Year 2
$ 60,000.00	1/1/01 - 12/31/01	Year 3

Summary: The goal of this research proposal is to gain a complete understanding of how DMD gene production is controlled in muscle, and to apply this knowledge to the development of effective gene transfer-based therapeutic strategies.

David MacLennan, Ph.D.
(RG) The genetic and pathophysiological basis of Brody disease, 
central core disease (CCD) and malignant hyperthermia (MH)
$ 60,000.00	1/1/00 - 12/31/00	Year 2
$ 60,000.00	1/1/01 - 12/31/01	Year 3

Summary: Our group will investigate the inheritance patterns and the cause of a group of muscle diseases that are characterized by abnormalities in calcium regulation; Brody disease, CCD and MH.

(SG) Gordon Research Conference on Muscle: 
Excitation-Contraction Coupling
$ 6,000.00	6/1/00 - 6/30/00	Year 1

Christopher E. Pearson, Ph.D.
(RG) Role of DNA replication and repair in 
the trinucleotide repeat instability
$ 90,000.00	7/1/99 - 6/30/00	Year 1
$ 90,000.00	7/1/00 - 6/30/01	Year 2
$ 90,000.00	7/1/01 - 6/30/02	Year 3

Summary: Our goal is to understand the mechanism of a DNA mutation responsible for MMD, CDM, OPMD and FRDA with the aim of being able to prevent or reverse the mutation allowing prevention or treatment of disease symptoms.

Winnipeg - University of Manitoba

Klaus Wrogemann, M.D., Ph.D.
(RG) Modifier genes in limb-girdle muscular 
dystrophy (LGMD) 2B/Miyoshi myopathy
$ 60,000.00	7/1/99 - 6/30/00	Year 1
$ 60,000.00	7/1/00 - 6/30/01	Year 2
$ 60,000.00	7/1/01 - 6/30/02	Year 3

Summary: LGMD2B and Miyoshi myopathy can be caused by identical mutations of the dysferlin gene. Researchers propose to identify additional genetic factors that determine which of the two diseases develop.

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