Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice

• DOI: 10.1073/pnas.1013067108
• Publication Date: 2010-12-28T01:45:14Z
• Authors: Alison R. Amenta; Atilgan Yilmaz; Sasha Bogdanovich; Beth A. McKechnie; Mehrdad Abedi; Tejvir S. Khurana; Justin R. Fallon
• Keywords: Biglycan; Utrophin; Sarcolemma; mdx mouse; Dysferlin

Duchenne muscular dystrophy (DMD) is caused by mutations in dystrophin and the subsequent disruption of dystrophin-associated protein complex (DAPC). Utrophin a homolog expressed at high levels developing muscle that an attractive target for DMD therapy. Here we show extracellular matrix biglycan regulates utrophin expression immature recombinant human (rhBGN) increases cultured myotubes. Systemically delivered rhBGN up-regulates sarcolemma reduces pathology mdx mouse model DMD. RhBGN treatment also improves function as judged reduced susceptibility to eccentric contraction-induced injury. required therapeutic effect. Several lines evidence indicate acts recruiting membrane. well tolerated animals dosed long 3 months. We propose could be therapy