Estudo das mutações da distrofia muscular de Becker faz antever um sucesso com o uso de oligonucleotídeos para salto de exon

Holanda – Quarenta e oito pacientes com distrofia muscular de Becker foram incluídos, o que representa 11 mutações diferentes. As alterações genéticas que eles apresentam serão as mesmas que os pacientes que se submeteram ou se submeterão ao salto de exon A idade média dos pacientes foi de 43 anos (variação 6-67). Nove pacientes eram usuários de cadeiras de rodas (26-56 anos). Cardiomiopatia dilatada estava presente em 7/36 pacientes. Apenas um paciente utilizava suporte ventilatório. Três pacientes morreram com a idade de 45, 50 e 76 anos, respectivamente. Portanto a severidade da distrofia muscular será amenizada com o uso de oligonucleotideos para salto de exon.

O resumo em inglês pode ser lido abaixo:

(J Neurol Psychiatry, May 2013) Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy

J C van den Bergen, S M Schade van Westrum, L Dekker, A J van der Kooi, M de Visser, B H A Wokke, C S Straathof, M A Hulsker, A Aartsma-Rus, J J Verschuuren, and H B Ginjaar

Abstract

Objective Duchenne and Becker muscular dystrophy (DMD/BMD) are both caused by mutations in the DMD gene. Out-of-frame mutations in DMD lead to absence of the dystrophin protein, while in-frame BMD mutations cause production of internally deleted dystrophin. Clinically, patients with DMD loose ambulance around the age of 12, need ventilatory support at their late teens and die in their third or fourth decade due to pulmonary or cardiac failure. BMD has a more variable disease course. The disease course of patients with BMD with specific mutations could be very informative to predict the outcome of the exon-skipping therapy, aiming to restore the reading-frame in patients with DMD.

Methods Patients with BMD with a mutation equalling a DMD mutation after successful exon skipping were selected from the Dutch Dystrophinopathy Database. Information about disease course was gathered through a standardised questionnaire. Cardiac data were collected from medical correspondence and a previous study on cardiac function in BMD

Results Forty-eight patients were included, representing 11 different mutations. Median age of patients was 43 years (range 6–67). Nine patients were wheelchair users (26–56 years). Dilated cardiomyopathy was present in 7/36 patients. Only one patient used ventilatory support. Three patients had died at the age of 45, 50 and 76 years, respectively

Conclusions This study provides mutation specific data on the course of disease in patients with BMD. It shows that the disease course of patients with BMD, with a mutation equalling a ‘skipped’ DMD mutation is relatively mild. This finding strongly supports the potential benefit of exon skipping in patients with DMD.