Key result
Ataluren fails to significantly attenuate cardiac and pulmonary decline in Duchenne muscular dystrophy.
Why the study?
Does Ataluren ameliorate disease progression in non-ambulatory patients with non-sense mutation Duchenne muscular dystrophy?
Case Report (n=4)
No
Does Ataluren ameliorate disease progression in non-ambulatory patients with non-sense mutation Duchenne muscular dystrophy?
p-value: p=not statistically significant
Off-label use of Ataluren in non-ambulatory nmDMD patients appears to mildly attenuate disease progression, including cardiac and pulmonary decline, with a good safety profile.
Should not change practice; hypothesis-generating for ataluren in non-ambulatory nmDMD and needs controlled trials.
About 15% of Duchenne muscular dystrophy (DMD) cases are caused by point mutations leading to premature stop codons and disrupted synthesis of the dystrophin protein. Stop codon read-through therapy is available with the drug Ataluren (Translarna® by PTC Therapeutics). Following positive results in ambulatory nmDMD (non-sense mutation Duchenne muscular dystrophy) patients, Ataluren received conditional approval in ambulant nmDMD patients by the EMA in 2014. However, there are limited data on non-ambulatory nmDMD patients treated with Ataluren. Here, we report our experience in four non-ambulatory nmDMD patients. Routine investigations included cardiac function, pulmonary function tests and muscle strength. We compared changes in left ventricular fractional shorting, forced volume vital capacity and BMI from two defined time periods (18-26-month period prior to and after Ataluren start). Mean age at loss of ambulation was 10.1 ± 0.5 years, mean age when initiating Ataluren treatment 14.1 ± 1.4 years. Serial echocardiography, pulmonary lung function tests, and assessment of muscle strength indicated mild attenuation of disease progression after initiation of Ataluren treatment. A possible side effect of Ataluren was a reduction in BMI. There were no adverse clinical effects or relevant abnormalities in routine laboratory values. We conclude that Ataluren appears to mildly ameliorate the clinical course in our patients with a good safety profile. However, larger clinical trials are required to assess the role of Ataluren and its long-term impact on disease progression in non-ambulant nmDMD patients.
No takes yet. Share an insight, caveat, or question.
Ebrahimi‐Fakhari et al. (2018) conducted a case report in Duchenne muscular dystrophy (n=4). Ataluren vs. Pre-treatment baseline was evaluated on Changes in left ventricular fractional shortening (LVFS) and forced volume vital capacity (FVC) (p=not statistically significant). Ataluren treatment in four non-ambulatory patients with Duchenne muscular dystrophy mildly attenuated the decline in cardiac and pulmonary function, though changes were not statistically significant.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: