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A new way to regulate the NMJ

Nature Medicine volume 13, pages 538–539 (2007)Cite this article

A key regulator of the neuromuscular junction, the transcriptional co-activator PGC-1α, is a potential target for Duchenne muscular dystrophy therapy.

This year marks the twentieth anniversary of the discovery of the dystrophin gene, which is mutated in the devastating X-linked recessive muscle disease Duchenne muscular dystrophy (DMD)1. During DMD, heart and skeletal muscles break down, so that the affected boys are typically wheelchair-bound by 12 years of age and die in their second or third decade of life. Currently, experimental strategies for DMD therapy consist of either replacement of dystrophin by gene therapy, or exclusion of the mutation through exon skipping using antisense oligonucleotides2. Early stage clinical trials using these targeted approaches are beginning. The replacement of the large cytoskeletal dystrophin gene in both skeletal and cardiac muscle, however, represents a major technical challenge. Other experimental strategies treat the symptoms of the disease with drugs such as myostatin blockers, for which clinical trials are ongoing3. Such drugs have the advantage of being easy to deliver to all muscle types, do not invoke an immune response and are relatively inexpensive4. In a recent report, Handschin et al. identify a new target for pharmacological therapy of DMD: peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)5.

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Figure 1: Model for the transcriptional activation by PGC-1α.

Kim Caesar

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Authors and Affiliations

  1. Departments of Physiology, Kay E Davies is at the MRC Functional Genetics Unit, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK. Kay.davies@dpag.ox.ac.uk,

    Kay E Davies

  2. Tejvir S Khurana is in the Department of Physiology and at the Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Richards Building, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA. tsk@mail.med.upenn.edu,

    Tejvir S Khurana

Authors
  1. Kay E Davies
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  2. Tejvir S Khurana
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Competing interests

K.E.D. is a major shareholder of VASTox plc., a company concerned with the development of treatments for muscular dystrophy.

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Davies, K., Khurana, T. A new way to regulate the NMJ. Nat Med 13, 538–539 (2007). https://doi.org/10.1038/nm0507-538

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