Pharmacological strategies for muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a fatal, genetic disorder whose relentless progression underscores the urgency for developing a cure. Although Duchenne initiated clinical trials roughly 150 years ago, therapies for DMD remain supportive rather than curative. A paradigm shift towards developing rational therapeutic strategies occurred with identification of the DMD gene. Gene- and cell-based therapies designed to replace the missing gene and/or dystrophin protein have achieved varying degrees of success. However, pharmacological strategies not designed to replace dystrophin per se appear promising, and can circumvent many hurdles hampering gene- and cell-based therapy. Here, we will review present pharmacological strategies, in particular those dealing with functional substitution of dystrophin by utrophin and enhancing muscle progenitor commitment by myostatin blockade, with a view toward facilitating drug discovery for DMD.
Department of Physiology & Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA. tsk@mail.med.upenn.edu
Tejvir S
TS
Khurana
Kay E
KE
Davies
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D016189:Dystrophin / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009136:Muscular Dystrophies / Q000188:drug therapy*; D011401:Promoter Regions, Genetic; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; D049411:Utrophin; D002118:Calcium