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Technology Insight: therapy for Duchenne muscular dystrophy—an opportunity for personalized medicine?

Nature Clinical Practice Neurology volume 4, pages 149–158 (2008)Cite this article

Abstract

Since the identification of dystrophin as the protein product of the Duchenne and Becker muscular dystrophy locus, many different mutations, encompassing the entire spectrum of gene mutations ranging from point mutations to large deletions, have been found. These discoveries have led to the investigation of a variety of methods aimed at the treatment of muscular dystrophy, including strategies for gene replacement, gene correction, and modification of the gene product. The preferred approach in each case depends on the nature of the gene defect. In this Review, we focus on methods that have been developed for gene correction and for the modification of gene products. This mutation-focused approach offers the opportunity for 'personalized' gene therapy for muscular dystrophy and might also be a logical strategy for the treatment of other genetic disorders.

Key Points

  • Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder of skeletal and cardiac muscle that is caused by mutations in the dystrophin gene

  • New approaches to the treatment of DMD are directed at the specific kind of mutation that the patient carries, thereby effectively creating 'personalized gene therapy'

  • Mutation-specific therapies for DMD can be divided broadly into those that focus on point mutations and those that focus on frameshift deletions

  • The main technologies to target point mutations involve small molecules that enable stop-codon suppression, and small oligonucleotides that elicit gene correction

  • The main technology targeted at frameshift deletions is the use of antisense oligonucleotides to induce exon skipping

  • The identification of the patients with DMD who are most likely to benefit from personalized therapy will be greatly enhanced by advances in rapid and accurate molecular diagnostics

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Figure 1: Therapeutic options for point mutations.
Figure 2: Therapeutic options for frameshift mutations.

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Authors and Affiliations

  1. LE Lim is a Staff Physician in the Neurology Service at the Veterans Affairs Palo Alto Health Care System, and TA Rando is Chief of Neurology at the Veterans Affairs Palo Alto Health Care System, and Associate Professor of Neurology and Neurological Sciences and Deputy Director of the Stanford Center on Longevity at Stanford University, Stanford, CA, USA.,

    Leland E Lim & Thomas A Rando

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  1. Leland E Lim
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Correspondence to Thomas A Rando.

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Lim, L., Rando, T. Technology Insight: therapy for Duchenne muscular dystrophy—an opportunity for personalized medicine?. Nat Rev Neurol 4, 149–158 (2008). https://doi.org/10.1038/ncpneuro0737

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