Resultados benéficos com o uso do ataluren em pacientes com distrofia muscular de Duchenne/Becker
USA – Ataluren tem sido testada para tratamento da mutação de ponto (mutação sem sentido) na distrofia muscular de Duchenne. Os resultados dos estudos experimentais já foram apresentados mas neste resumos novas análises são feita sobre os efeitos a droga. Os pacientes tratados com doses mais baixas tiveram melhor resultado no teste da caminhada de 6 minutos mas também apresentaram menor quantidade de quedas acidentais.
O resumo em inglês pode ser lido abaixo:
(Annals of Neurology Vol 70 (suppl 15) 2011) Improvements in muscle function and accidental falling in Ataluren-treated patients with nonsense mutation dystrophinopathy (Duchenne/Becker Muscular Dystrophy – nmDBMD)
Russman BS (Portland, OR), Mathews KD (Iowa City, IA),Sampson JB (Salt Lake City, UT), Renfroe JB (Gulf Breeze,FL), Morsy MA, Elfring GL, Barth JA, Peltz SW(South Plainfield, NJ)
Objective: Dystrophinopathy patients progressively lose muscle function and become susceptible to accidental falling, the most common cause of limb fractures in this population. Ataluren is an investigational drug designed to overcome the effects of nonsense mutations, which are responsible for 13% of dystrophinopathy cases. In a pivotal trial in nmDBMD, low-dose ataluren demonstrated a clinically meaningful difference (29.7m) in change in 6-minute walk distance (6MWD) versus placebo (p=0.0584; post-hoc analysis). Secondary endpoints included timed function tests and patient/parentreported accidental falling. Methods: Males 5 yr of age with nmDBMD were stratified by age, corticosteroid use, and baseline 6MWD;randomized 1:1:1 to placebo; low-dose ataluren (10,10,20 mg/kg); or high-dose ataluren (20,20,40 mg/kg) orally TID; and evaluated every 6 wks for 48 wks. Results: The study enrolled 174 subjects (median [range] age=8 [5–20] yr, corticosteroid use=123/174 [71%], median [range] baseline 6MWD=360 [75–554] m). Differences in mean changes from baseline to Week 48 for low dose versus placebo were -2.40s stair ascend, -1.62s stair descend, -1.35s 10-m walk/run, and -0.01s stand from supine. Over 48 weeks, accidental falling declined in the low-dose arm versus placebo (relative ratio=0.37; post-hoc analysis). High dose-treated subjects with approximate peak plasma concentrations similar to low dose-treated subjects generally had outcomes similar to low dose-treated subjects. Conclusions: Subjects treated with ataluren 10,10,20 mg/kg experienced trends toward improvements in timed function tests and had fewer accidental falls versus placebo. These findings support the primary endpoint (6MWD) results showing a positive treatment effect for low-dose ataluren in this population.
