P.20.14 Non ambulant patients with deletion treatable by exon skipping 53 present a more severe phenotype than the general Duchenne population

Servais, Laurent; Seferian, A.; Yahou, R. Ben; Leturcq, F.; Zehrouni, K.; Benali, M.; Decostre, V.; Delahais, Virginie; Butoianu, Nina; Cuisset, J.M.; Cancés, Claude; Moing, A.G. Le; Laugel, Vincent; Klein, Andrea; Sabouraud, Pascal; Guiner, Caroline Le; Moullier, P.; Moraux, A.; Hogrel, Jean‐Yves; Montus, M.; Voït, Thomas

doi:10.1016/j.nmd.2013.06.704

Cited by 2 publications

(1 citation statement)

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“…The results of this study are consistent with this observation, as we could not detect a significant difference at 12 months, but only at 24 months. Similarly, Servais et al 37 reported that patients treatable by exon 53 skipping have a more severe phenotype when upper limb function was assessed in a cohort of 14 DMD; additionally, LOA had occurred 1 year earlier in 90 boys, 53 skippable, when compared with 400 other boys with DMD. Residual dystrophin level can partially explain such an observed phenomenon.…”

Section: Discussionmentioning

confidence: 92%

The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials

Ricotti

Ridout

Pane

et al. 2015

J Neurol Neurosurg Psychiatry

125

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ObjectiveWith the emergence of experimental therapies for Duchenne muscular dystrophy (DMD), it is fundamental to understand the natural history of this disorder to properly design clinical trials. The aims of this study were to assess the effects produced on motor function by different DMD genotypes and early initiation of glucocorticoids.MethodsThrough the NorthStar Network, standardised clinical data including the NorthStar Ambulatory Assessment score (NSAA) on 513 ambulant UK boys with DMD were analysed from 2004 to 2012. For the analysis of the genetic subpopulation, we also included data from 172 Italian boys with DMD. NSAA raw scores were converted into linear scores.ResultsOn the linearised NSAA, we observed an average decline of 8 units/year (4 units on raw NSAA analysis) after age 7. The median age at loss of ambulation (LOA) was 13 years (95% CI 12.1 to 13.5); 2 years prior to LOA, the estimated mean linearised NSAA score was 42/100 (13/34 raw scale). Starting glucocorticoids between 3 and 5 years conferred an additional gain in motor function of 3 units/year (1.3 raw units) up to age 7. When analysing the effect of genotype in the UK and Italian cumulative cohorts, individuals with deletions amenable to exons 44 and 46 skipping declined at a slower rate over 2 years (9 units (4 raw units), p<0.001), while 53 and 51 skippable deletions showed a faster decline of 14 (4.5; p<0.001) and 5 linearised units (2.4 NSAA units; p=0.02), respectively.ConclusionsOur study provides a novel insight on the current natural history of DMD, which will be instrumental for the design of future clinical trials.

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Section: Discussionmentioning

confidence: 92%