Therapeutic restoration of dystrophin expression in Duchenne muscular dystrophy

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 sig...

Full description

Saved in:
Bibliographic Details
Published in:Journal of muscle research and cell motility 2006-05, Vol.27 (5-7), p.387-398
Main Author: Wells, Dominic J
Format: Article
Language:English
Subjects:
Animals
Disease Models, Animal
Drug Evaluation, Preclinical
Dystrophin - biosynthesis
Dystrophin - genetics
Dystrophin - metabolism
Gene Expression - drug effects
Genes
Genetic Therapy
Genetic Vectors
Humans
Muscular dystrophy
Muscular Dystrophy, Duchenne - physiopathology
Muscular Dystrophy, Duchenne - therapy
Oligonucleotides, Antisense - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0142-4319
1573-2657
DOI:10.1007/s10974-006-9081-6