Non-ambulant Duchenne patients theoretically treatable by Exon 53 skipping have severe phenotype

International audienceBackground: Exon skipping therapy is an emerging approach in Duchenne Muscular Dystrophy (DMD). Antisense oligonucleotides that induce skipping of exon 51, 44, 45, or 53 are currently being evaluated in clinical trials. These trials were designedon the basis of data available in general DMD population.Objectives: Our objective was to compare the clinical and functional statuses of non-ambulant DMD patients theoreticallytreatable by exon 53 skipping and of DMD patients with other mutations.Methods: We first compared fifteen non-ambulant DMD patients carrying deletions theoretically treatable by exon 53 skipping(DMD-53) with fifteen closely age-matched DMD patients with mutations not treatable by exon 53 skipping (DMD-all-non-53)then with fifteen DMD patients carrying deletions not treatable by exon 53 skipping (DMD-del-non-53).Results: We found that DMD-53 patients had a lower left ventricular ejection fraction, more contractures and they tend to haveweaker grips and pinch strengths than other DMD patients. DMD-53 patients lost ambulation significantly younger than otherDMD patients. This result was confirmed by comparing ages at loss of ambulation in all non-ambulant DMD patients of theDMD cohort identified in a molecular diagnostic lab