Therapeutic restoration of dystrophin expression in Duchenne muscular dystrophy

Original Paper

Abstract

It is 20 years since the discovery of the genetic defect causing Duchenne muscular dystrophy (DMD). This X-linked progressive and fatal myopathy is due to the absence of a functional version of a critical sub-sarcolemmal protein called dystrophin that appears to act both as a structural and as a signalling molecule in the muscle fibre. A number of molecular approaches have been developed to restore the expression of dystrophin in DMD patients. Pre-clinical experiments have demonstrated the potential of delivery of recombinant versions of the DMD gene using viral or non-viral vectors and importantly several of these systems are compatible with vascular delivery, an essential feature as all muscles are affected in this condition. Other studies have shown that antisense oligonucleotides can modify the splicing of the primary transcript to provide an internally truncated but still functional protein. Alternatively, in approximately 10–20% of cases it is possible to chemically persuade the translational machinery to read-through a pre-mature stop codon. The pre-clinical results of the last 4 years have encouraged the development of clinical trials for all of the above.

Keywords

Duchenne muscular dystrophy Dystrophin Animal models mdx Antisense oligonucleotides Exon skipping Viral vectors Non-viral vectors Gene therapy 

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Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  1. 1.Gene Targeting Group, Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College LondonCharing Cross HospitalLondonUK

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