Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy

Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well‐characterized cohort of 10–18 year‐old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC). The fraction of the maximum flow that is not used during tidal breathing has been termed inspiratory flow reserve (IFR). DMD patients in both treatment groups of DELOS (idebenone, n = 31; placebo: n = 33) had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by −0.29 L/sec in patients on placebo (95%CI: −0.51, −0.08; P = 0.008 at week 52), whereas it remained stable in patients on idebenone (change from baseline to week 52: 0.01 L/sec; 95%CI: −0.22, 0.24; P = 0.950). The between‐group difference favoring idebenone was 0.27 L/sec (P = 0.043) at week 26 and 0.30 L/sec (P = 0.061) at week 52. In addition, during the study period, IFR improved by 2.8% in patients receiving idebenone and worsened by −3.0% among patients on placebo (between‐group difference 5.8% at week 52; P = 0.040). Although the clinical interpretation of these data is currently limited due to the scarcity of routine clinical practice experience with dynamic inspiratory function outcomes in DMD, these findings from a randomized controlled study nevertheless suggest that idebenone preserved inspiratory muscle function as assessed by V'I,max(FVC) and IFR in patients with DMD

DIAGNOSIS OF BECKER MUSCULAR DYSTROPHY: RESULTS OF RE-ANALYSIS OF DNA SAMPLES

Item does not contain fulltextINTRODUCTION: The phenotype of Becker muscular dystrophy (BMD) is highly variable, and the disease may be underdiagnosed. We searched for new mutations in the DMD gene in a cohort of previously undiagnosed patients who had been referred in the period 1985-1995. METHODS: All requests for DNA analysis of the DMD gene in probands with suspected BMD were re-evaluated. If the phenotype was compatible with BMD, and no deletions or duplications were detected, DNA samples were screened for small mutations. RESULTS: In 79 of 185 referrals, no mutation was found. Analysis could be performed on 31 DNA samples. Seven different mutations, including 3 novel ones, were found. Long-term clinical follow-up is described. CONCLUSIONS: Refining DNA analysis in previously undiagnosed cases can identify mutations in the DMD gene and provide genetic diagnosis of BMD. A delayed diagnosis can still be valuable for the proband or the relatives of BMD patients. Muscle Nerve 53: 44-48, 2016

Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy

Decline in respiratory function in patients with DMD starts during early teenage years and leads to early morbidity and mortality. Published evidence of efficacy for idebenone on respiratory function outcomes is currently limited to 12 months of follow-up time. Here we report data collected as retrospective cohort study (SYROS) from 18 DMD patients not using glucocorticoids who were treated with idebenone (900 mg/day) under Expanded Access Programs (EAPs). The objective was to assess the long-term respiratory function evolution for periods On-Idebenone compared to periods Off-Idebenone in the same patients. The mean idebenone exposure in the EAPs was 4.2 (range 2.4–6.1) years. The primary endpoint was the annual change in forced vital capacity percent of predicted (FVC%p) compared between Off-Idebenone and On-Idebenone periods. The annual rate of decline in FVC%p was reduced by approximately 50% from −7.4% (95% CI: −9.1, −5.8) for the Off-Idebenone periods to −3.8% (95% CI: −4.8, −2.8) for the On-Idebenone periods (N = 11). Similarly, annual change in peak expiratory flow percent of predicted (PEF%p) was −5.9% (95% CI: −8.0, −3.9) for the Off-Idebenone periods (N = 9) and reduced to −1.9% (95% CI: −3.2, −0.7) for the On-Idebenone periods during the EAPs. The reduced rates of decline in FVC%p and PEF%p were maintained for several years with possible beneficial effects on the rate of bronchopulmonary adverse events, time to 10% decline in FVC%p and risk of hospitalization due to respiratory cause. These long-term data provide Class IV evidence to further support the disease modifying treatment effect of idebenone previously observed in randomized, controlled trials