G.P.211: Combination therapy with Glatiramer acetate and FTS improves strength and fibrosis in the dy2J/dy2Jmouse model of MDC1A

Abstract

Merosin deficient congenital muscular dystrophy type 1A (MDC1A) is a devastating incurable disorder of childhood. We previously studied the effect of Glatiramer acetate (GA), an anti-inflammatory agent and S- farnesylthiosalicilate acid (FTS), an anti-fibrotic agent, as a single agent in the dy2J/dy2J mouse model of MDC1A. Each of the two medications showed a different pattern of disease on three primary outcome measures: strength, fibrosis and animal mobility. GA monotheraphy resulted in significant improvement in hind limb muscle strength and movement parameters, but without a decrease in fibrosis measurement. FTS monotheraphy was associated with increased hind limb muscle strength, decreased fibrosis, but with no improvement in movement parameters. In the present study, the combination of GA and FTS was found to increase both fore (32%) and hind limb (75.8%) muscle strength, more than treatment with either drug alone (fore limb: no significant change for GA and for FTS; hind limb: GA 52.7% vs. FTS 42%). In addition, GA-FTS treatment resulted in significant reduction in muscle fibrosis (35.4%) compared to untreated dy2J/dy2J mice. However, no improvement in animal mobility was shown. According to the results, combined GA and FTS increased both fore and hind limb muscle strength more than either drug by itself and significantly ameliorated muscle fibrosis. Thus, GA-FTS treatment might be considered as a potential candidate for future clinical trials in children with CMD.