Congenital muscular dystrophies: toward molecular therapeutic interventions.
Congenital muscular dystrophies (CMDs) are a clinically and genetically heterogeneous group of neuromuscular disorders that typically present at birth or in early infancy with hypotonia, weakness, and histologic evidence of a dystrophic myopathy. CMD biochemical types include various abnormalities of alpha-dystroglycan O-mannosyl glycosylation as well as defects in integrin matrix receptors, the extracellular matrix proteins laminin-alpha(2) and collagen VI, nuclear proteins such as lamin A/C, and a protein of the endoplasmic reticulum, selenoprotein N. Current therapies are directed mostly at supportive care; however, recent advances in biotechnology and increased knowledge of the pathophysiology underlying the various CMD types have helped identify potential therapeutic strategies directed at genetic, molecular, and biochemical pathways involved in these disorders. In this article, we review our current understanding of the molecular pathogenesis of several CMD types and how these mechanisms may be therapeutically targeted.
Collins
James
J
Division of Neurology, Cincinnati Children's Hospital Medical Center, MLC 2015, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. james.collins@cchmc.org
Bönnemann
Carsten G
CG
D015703:Antigens, CD / Q000235:genetics; D024142:Collagen Type VI / Q000172:deficiency / Q000235:genetics; D049030:Dystroglycans / Q000172:deficiency / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D039001:Integrin alpha Chains / Q000172:deficiency / Q000235:genetics; D007797:Laminin / Q000172:deficiency / Q000235:genetics; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D009136:Muscular Dystrophies / Q000151:congenital / Q000235:genetics / Q000628:therapy; D009154:Mutation / Q000235:genetics; D051140:Selenoproteins / Q000172:deficiency / Q000235:genetics
D015703:Antigens, CD; D024142:Collagen Type VI; D039001:Integrin alpha Chains; D007797:Laminin; D009124:Muscle Proteins; C435489:SELENON protein, human; D051140:Selenoproteins; C085725:integrin alpha7; C102645:laminin alpha 2; D049030:Dystroglycans