Utrophin upregulation for treating Duchenne or Becker muscular dystrophy: how close are we?
Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder for which there is currently no effective treatment. This disorder is caused by mutations or deletions in the gene encoding dystrophin that prevent expression of dystrophin at the sarcolemma. A promising pharmacological treatment for DMD aims to increase levels of utrophin, a homolog of dystrophin, in muscle fibers of affected patients to compensate for the absence of dystrophin. Here, we review recent developments in our understanding of the regulatory pathways that govern utrophin expression, and highlight studies that have used activators of these pathways to alleviate the dystrophic symptoms in DMD animal models. The results of these preclinical studies are promising and bring us closer to implementing appropriate utrophin-based drug therapies for DMD patients.
Miura
Pedro
P
Department of Cellular and Molecular Medicine and Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
Jasmin
Bernard J
BJ
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000628:therapy*; D050778:NFATC Transcription Factors / Q000378:metabolism; D020890:Neuregulin-1 / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D015854:Up-Regulation; D049411:Utrophin / Q000235:genetics / Q000378:metabolism*
D016189:Dystrophin; D050778:NFATC Transcription Factors; D020890:Neuregulin-1; D049411:Utrophin; D009569:Nitric Oxide; D019703:Calcineurin