Progress in therapeutic antisense applications for neuromuscular disorders.
Neuromuscular disorders are a frequent cause of chronic disability in man. They often result from mutations in single genes and are thus, in principle, well suited for gene therapy. However, the tissues involved (muscle and the central nervous system) are post-mitotic, which poses a challenge for most viral vectors. In some cases, alternative approaches may use small molecules, for example, antisense oligonucleotides (AONs). These do not deliver a new gene, but rather modulate existing gene products or alter the utilization of pathways. For Duchenne muscular dystrophy, this approach is in early phase clinical trials, and for two other common neuromuscular disorders (spinal muscular atrophy and myotonic dystrophy), significant preclinical advances have recently been made.
Aartsma-Rus
Annemieke
A
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. a.m.rus@lumc.nl
van Ommen
Gert-Jan B
GJ
D000818:Animals; D016189:Dystrophin / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005091:Exons / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D023421:Models, Animal; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy / Q000235:genetics; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009223:Myotonic Dystrophy / Q000188:drug therapy / Q000235:genetics; D009468:Neuromuscular Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use*; D012322:RNA Precursors / Q000235:genetics; D014158:Transcription, Genetic
D016189:Dystrophin; D016376:Oligonucleotides, Antisense; D012322:RNA Precursors