Inherited Muscle Disease: Gene Therapy

Abstract

Muscular dystrophies have been an area of special interest for genetic therapies. The abundance of skeletal muscle tissue in the body presents particular problems for this form of treatment.

Keywords: muscular dystrophy; duchenne; dystrophin; gene therapy; cell transfer

Figure 1.

Hypothetical view of the dystrophin‐associated complex of proteins and glycoproteins at the surface of the muscle fibre. Dystrophin, the protein that is lacking in Duchenne muscular dystrophy and is defective in the milder Becker muscular dystrophy, appears to be the key protein required for effective assembly of this complex, elucidation of which has proved an interesting example of the interaction between positional cloning and biochemical investigation. Mutations in the genes for the various sarcoglycans have been found to underlie some of the limb‐girdle muscular dystrophies (LGMD): α‐Sarcoglycan – LGMD 2D, β‐Sarcoglycan – LGMD 2E, γ‐Sarcoglycan – LGMD 2C, δ‐Sarcoglycan – LGMD 2F. A large proportion of congenital muscular dystrophy cases have proved to involve mutations in the α‐chain of merosin, the link of this complex into the basement membrane. The muscle‐specific isoform of neural nitric oxide synthase, μNOS, and the dystrophin‐like protein, dystroglycan, are also linked into this complex and disruption of this complex may compromise their functions and perhaps contribute to some aspects of the pathology of the dystrophinopathies. Other dystrophies are ascribed to proteins that do not appear to be part of this complex, some associated with the cell surface, some with the nuclear membranes and some with the sarcoplasm (for review, see Cohn and Campbell (2000) Molecular basis of muscular dystrophies. Muscle and Nerve 23: 1456–1471).

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Dystrophin (muscular dystrophy, Duchenne and Becker types) (DMD); Locus ID: 1756. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1756

Dystrophin (muscular dystrophy, Duchenne and Becker types) (DMD); MIM number: 300377. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?300377

Exon skipping with 2′O‐methyl phosphorothioate antisense oligonucleotides to restore open reading frame in the mutated dystrophin gene http://hdl.handle.net/1887/604

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Partridge, Terence(Sep 2007) Inherited Muscle Disease: Gene Therapy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005753.pub2]