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Congenital Muscular Dystrophies: Toward Molecular Therapeutic Interventions

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Abstract

Congenital muscular dystrophies (CMDs) are a clinically and genetically heterogeneous group of neuromuscular disorders that typically present at birth or in early infancy with hypotonia, weakness, and histologic evidence of a dystrophic myopathy. CMD biochemical types include various abnormalities of α-dystroglycan O-mannosyl glycosylation as well as defects in integrin matrix receptors, the extracellular matrix proteins laminin-α2 and collagen VI, nuclear proteins such as lamin A/C, and a protein of the endoplasmic reticulum, selenoprotein N. Current therapies are directed mostly at supportive care; however, recent advances in biotechnology and increased knowledge of the pathophysiology underlying the various CMD types have helped identify potential therapeutic strategies directed at genetic, molecular, and biochemical pathways involved in these disorders. In this article, we review our current understanding of the molecular pathogenesis of several CMD types and how these mechanisms may be therapeutically targeted.

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Acknowledgments

The authors thank Dr. A. Reghan Foley and Dr. Anne Rutkowski for their helpful comments regarding the manuscript. Dr. Bönnemann is supported by grants from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR051999) and from MDA USA (MDA3896).

Disclosure

Dr. Collins receives research funding from Cure CMD (not-for-profit patient advocacy). Dr. Bönnemann is an investigator on PTC124 trials (2a and 2b) in patients with Duchenne muscular dystrophy (PTC Therapeutics).

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  1. Division of Neurology, Cincinnati Children’s Hospital Medical Center, MLC 2015, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA

    James Collins

  2. The Children’s Hospital of Philadelphia, Division of Neurology, Abramson Research Center, Room 516I, 34th Street and Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Carsten G. Bönnemann

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Correspondence to Carsten G. Bönnemann.

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Collins, J., Bönnemann, C.G. Congenital Muscular Dystrophies: Toward Molecular Therapeutic Interventions. Curr Neurol Neurosci Rep 10, 83–91 (2010). https://doi.org/10.1007/s11910-010-0092-8

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