The Ilsa Mae Research Fund and Muscular Dystrophy Canada are pleased to announce that matching funds for a $1 million (CAD), 3 country research project have been secured.   This is proof of no matter how small the donation, every dollar is one dollar closer to a cure.

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E-Rare-2: Innovative Therapeutic Approaches 

Common Pathogenic Pathways and Therapeutics for SMA and ALS motoneuron diseases

Term of project: 2014-2017

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.

Lead Investigators:

Cédric Raoul (Project Coordinator)
INM, Inserm UMR105
Montpellier
France

Rashmi Kothary
Ottawa Hospital Research Institute, Department of Regenerative Medicine
Ottawa, Canada

Patrick Aebischer
Swiss Federal Institute of Technology, Brain Mind Institute
Lausanne, Switzerland

Funding partners:

CIHR’s Institute of Genetics, $390,150
Muscular Dystrophy Canada, Ilsa Mae Fund, $300,000
Swiss National Science Foundation, $292,563

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