Abstract
IntroductionAtaluren is a relatively new treatment for male patients with Duchenne muscular dystrophy (DMD) due to a premature stop codon. Long-term longitudinal data as well as efficacy data on non-ambulant patients are still lacking. Here we present the results from a long-term follow-up study of all DMD patients treated with ataluren and followed at the Queen Silvia Children’s Hospital in Gothenburg, Sweden, with focus on the evolution of patients’ upper motor and respiratory function over time.MethodsThis is a retrospective longitudinal case-series study of all male DMD patients treated with ataluren and followed at the Queen Silvia Children’s Hospital in Gothenburg, Sweden, since 2008.ResultsOur eleven patients had a median exposure to ataluren of 2312 days which is almost a fourfold higher than previous studies. Loss of ambulation occurred at a median age of 13.2 years. Patients who lost ambulation prior to 13.2 years of age had received ataluren for 5 years, whereas patients who continued to be ambulatory after 13.2 years of age had received ataluren for 6.5 years until loss of ambulation or last follow-up if still ambulatory. Four of six non ambulatory patients had Performance of the Upper Limb scores above the expected mean values over time. All but one patient maintained a pulmonary decline above the expected over time. All ambulatory patients increased in their predicted forced vital capacity (FVC) with 2.8 to 8.2% annually. Following loss of ambulation, 5 of 6 patients declined in predicted FVC (%), with annual rate of decline varying from 1.8 to 21.1%. The treatment was safe and well tolerated throughout the follow-up period.ConclusionsThis is the first study to present long-term cumulative treatment outcomes over a median period of 6.3 years on ataluren treatment. Our results indicate a delay in loss of ambulation, as well as a slower decline in FVC and upper limb motor function even after loss of ambulation. We suggest that treatment with ataluren should be initiated as soon as the diagnosis is confirmed, closely monitored and, in case of sustainable benefit, continued even after loss of ambulation.
Highlights
Ataluren is a relatively new treatment for male patients with Duchenne muscular dystrophy (DMD) due to a premature stop codon
Duchenne muscular dystrophy (DMD) is an X-linked, progressive neuromuscular disorder mainly affecting males, with symptom onset around 2–3 years of age
In 10–15% of patients with DMD the cause is nonsense mutations leading to premature stop codons in the reading frame of the dystrophin gene, resulting in truncated dystrophin protein [5, 6]
Summary
Ataluren is a relatively new treatment for male patients with Duchenne muscular dystrophy (DMD) due to a premature stop codon. The rehabilitation includes physiotherapy, occupational therapy and psychosocial intervention These are initiated as soon as the diagnosis is established and reevaluated 1–2 times per year, in order to help patients develop and maintain motor functions and prevent development of contractures, scoliosis and other irreversible symptoms due to the disease progression [4]. In recent years a small nonaminoglycoside molecule, known as ataluren, has been developed which promotes readthrough of the premature stop codon in the mRNA and dystrophin expression [7, 8] Studies have shown this to be a safe and effective treatment, that seems to slow down the disease progression if given early in the disease course [5, 8, 9]. Ataluren is approved by the European Medicine Agency (EMA) for the treatment of male patients older than 2 years of age with DMD caused by a premature stop codon
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