Premium
Activin IIB receptor blockade attenuates dystrophic pathology in a mouse model of duchenne muscular dystrophy
Author(s) -
Morine Kevin J.,
Bish Lawrence T.,
Selsby Joshua T.,
Gazzara Jeffery A.,
Pendrak Klara,
Sleeper Meg M.,
Barton Elisabeth R.,
Lee SeJin,
Sweeney H. Lee
Publication year - 2010
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21743
Subject(s) - myostatin , duchenne muscular dystrophy , endocrinology , activin receptor , medicine , muscular dystrophy , transforming growth factor , mdx mouse , acvr2b , itga7 , receptor , skeletal muscle , biology , neuromuscular blockade , tgf beta signaling pathway , dystrophin , anesthesia
Modulation of transforming growth factor‐β (TGF‐β) signaling to promote muscle growth holds tremendous promise for the muscular dystrophies and other disorders involving the loss of functional muscle mass. Previous studies have focused on the TGF‐β family member myostatin and demonstrated that inhibition of myostatin leads to muscle growth in normal and dystrophic mice. We describe a unique method of systemic inhibition of activin IIB receptor signaling via adeno‐associated virus (AAV)‐mediated gene transfer of a soluble form of the extracellular domain of the activin IIB receptor to the liver. Treatment of mdx mice with activin IIB receptor blockade led to increased skeletal muscle mass, increased force production in the extensor digitorum longus (EDL), and reduced serum creatine kinase. No effect on heart mass or function was observed. Our results indicate that activin IIB receptor blockade represents a novel and effective therapeutic strategy for the muscular dystrophies. Muscle Nerve, 2010