Nova droga experimental para tratamento da mutação de ponto (mutação sem sentido) da distrofia muscular de Duchenne
Japão – este grupo de pesquisadores tem uma longa lista de pesquisas utilizando antibióticos aminoglicosídeos na mutação de ponto da distrofia muscular de Duchenne. Na pesquisa atual eles tem resultados animadores com um novo aminoglicosídeo semi-sintético a arbekacina.
O resumo em inglês que será apresentado em dezembro pode ser lido abaixo:
(ASCB 2011, Denver – Colorado) Arbekacin as a therapeutic readthrough inducer for treatment of nonsense mutation-mediated Duchenne muscular dystrophy
M. Shiozuka, A. Nishida, M. Matsuo, M. Yoshida, Y. Nonomura, R. Matsuda – Japan
Translational readthrough of a premature termination codon is a promising therapeutic method in more than 2,400 distinctly inherited human diseases. We previously reported that negamycin, a dipeptide antibiotic, that binds to the ribosomal decoding site and alters translational accuracy, successfully restored dystrophin expression with less toxicity than gentamicin in mdx mouse, which carries a premature termination codon in the dystrophin gene. In order to measure translational readthrough activity with quantitative accuracy, we established a novel transgenic mouse strain, named READ (Readthrough Evaluation and Assessment by Dual reporter). We found that arbekacin induced the in vivo nonsense suppression in READ mice dose-dependently, and promotes the accumulation of ystrophin, reduction of serum creatine kinase activity and improvement of contractile function in mdx mice. Moreover, arbekacin exhibits restoration of dystrophin expression on muscle cell obtained by biopsies from Duchenne muscular dystrophy patients caused by nonsense mutations. We have validated the efficacy of arbekacin on dystrophin-deficient muscle that we ultimately wish to treat. Arbekacin is a brekthrough readthrough-inducing drug for muscular dystrophy patients harboring nonsense mutations. This work was supported in part by The Ichiro Kanehara Foundation (to MS), Fugaku Foundation (to MS), Health and Labour Sciences Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health (19A-020; to RM), Comprehensive Research on Disability Health and Welfare (H22-ShinkeiKin-Ippan-016; to RM), Nervous and Mental Disorders (20B-13; to RM) from the Ministry of Health, Labour and Welfare, Japan.
