What is the impact of gene therapy on Duchenne muscular dystrophy?

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Mendell JR, Goemans N, Lowes LP, et al; Eteplirsen Study Group and Telethon Foundation DMD Italian Network

Ann Neurol 2016; 79:257-271.



To continue evaluation of the long-term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three-year progression of eteplirsen-treated patients was compared to matched historical controls (HC).


Ambulatory DMD patients who were ≥7 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open-label basis. The primary functional assessment in this study was the 6-Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype.


At 36 months, eteplirsen-treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen-treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.


Over 3 years of follow-up, eteplirsen-treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC.


You may also check the following for concerns raised about the safety of Eteplirsen:

Approving a problematic muscular dystrophy drug: implications for FDA policy.

Kesselheim AS, Avorn J.

JAMA 2016; 316:2357-2358.


Both references are now included in the neurochecklist:

Duchenne muscular dystrophy (DMD): management


Abstract link

One and done gene therapy. NIH Image Gallery on Flikr. https://www.flickr.com/photos/nihgov/23000041831
One and done gene therapy. NIH Image Gallery on Flikr. https://www.flickr.com/photos/nihgov/23000041831

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