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Involvement of metabolic remodeling in the development of the dystrophic phenotype in dysferlinopathies

Research Project
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01.06.2020
 - 31.05.2021

Dysferlinopathies are muscular dystrophies that are caused by a mutation in the dysferlin gene. Dysferlin plays a prominent role in membrane repair and dysferlin-deficient muscles develop a progressive muscular dystrophy. Currently, effective treatments for dysferlinopathies are lacking. Unexpectedly, even though experimental approaches can successfully restore membrane repair, muscles remain dystrophic, suggesting that additional, so-far unknown dysferlin-dependent functions might be involved in the development of the pathological phenotype. Therefore, alternative or complementary therapeutic interventions are needed. In many muscle diseases including Duchenne muscular dystrophy, overexpression of PGC-1α (peroxisome proliferator‐activated receptor γ coactivator 1α) in skeletal muscle ameliorates muscle fiber atrophy, integrity and function. Therefore, we were interested in the potential therapeutic effect of muscle PGC-1α on dysferlinopathy. Surprisingly however, the pathology of dysferlin-deficient mice was exacerbated by elevated levels of PGC-1α. Our experiments furthermore revealed an altered metabolic phenotype in dysferlin-deficient muscles, which might contribute to disease etiology and progression. To elucidate the implications of these observations, our projects aims at further unraveling the involvement of this metabolic remodeling in the development of the dystrophic phenotype. A better understanding of the disease patho-etiology could open novel therapeutic avenues to treat this muscular dystrophy.

Funding

Involvement of metabolic remodeling in the development of the dystrophic phenotype in dysferlinopathies

Foundations / Associations (GrantsTool), 06.2020-05.2021 (12)
PI : Furrer, Regula.

Members (1)

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Regula Furrer

Principal Investigator