Imatinib melhora as alterações patológicas dos camundongos com uma forma grave de distrofia muscular e inibe a expressão de marcadores de fibrose nas células tronco mesenquimais
Japão – A droga imatinib é usada em alguns tipos de câncer. Estudada em camundongos no Brasil já demonstrou sua capacidade de melhorar as alterações patológicas da distrofia muscular. Nesta pesquisa a droga foi utilizada em camunndongos com forma mais grave de distrofia muscular e também conseguiu reduzir as alterações patológicas. Além disso a droga foi testada em células tronco mesenquimais e conseguiu reduzir a expressão de marcadores de fibrose e sem impedir a proliferação de mioblastos, podendo ser útil no tratamento da doença.
O resumo em inglês pode ser lido abaixo:
(Neuromuscular Disorders, 2013) Imatinib attenuates dystrophic condition in severe mouse dystrophy and inhibits both proliferation and fibrosis-marker expression in muscle mesenchymal progenitors
Takahito Ito, Ryo Ogawa, Akiyoshi Uezumi, Takuji Ohtani, Yoko Watanabe, Kazutake Tsujikawa, Yuko Miyagoe-Suzuki, Shin’ichi Takeda, Hiroshi Yamamoto, So-ichiro Fukada – Japan
Imatinib mesylate inhibits signaling of tyrosine kinase receptors, including PDGFRa, and has been used for human cancer therapy.
Recent studies have indicated that imatinib is also effective in treatment of some chronic diseases with fibrosis. Fibrosis is the feature of Duchenne muscular dystrophy. It has been reported that imatinib attenuates fibrosis in mdx mice. Recently we revealed that PDGFRa is specifically expressed in muscle mesenchymal progenitors, which are the origin of muscle fibrosis. Here, we show that imatinib ameliorates the muscular pathology of DBA/2-mdx, a more severe mouse muscular dystrophy. In addition, imatinib inhibits both the proliferation and fibrosis marker expression induced by PDGF-AA in muscle mesenchymal progenitors in vitro. Importantly, the effective dose of imatinib on muscle mesenchymal progenitors did not inhibit myoblast proliferation. These results suggest that imatinib targes mesenchymal progenitors, and that a therapeutic strategy targeting mesenchymal progenitors could be a potential treatment for muscular dystrophies.
