Residual very low dystrophin levels mitigate dystrophinopathy towards Becker muscular dystrophy - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2018

Residual very low dystrophin levels mitigate dystrophinopathy towards Becker muscular dystrophy

Résumé

Novel therapy approaches for Duchenne Muscular Dystrophy aim at restoring dystrophin expression. However, the minimal dystrophin restoration levels required to achieve clinical benefit remains unknown. Residual dystrophin expression can be observed in certain patients carrying DMD intronic (including splice sites) and non-sense mutations in exons for which deletion leads to in-frame transcripts. To determine whether expression of very low dystrophin levels (<5%) can mitigate disease severity, residual dystrophin expression was correlated with disease severity of patients with these DMD mutations. Eighty patients were identified using the UMD-DMD-France database. Clinical data were obtained from medical care centres. Residual dystrophin expression was semi-quantitatively determined on Western Blots. Time-to-event analysis was performed for age of loss-of-ambulation as well as for respiratory, cardiac and orthopaedic endpoints and life expectancy. Patients with <5% dystrophin expression ambulated longer (n=33; median 45.6 years) than patients without dystrophin (n=47; median 10.3 years), (p<0.0001). Furthermore, patients with <5% dystrophin had longer survival (p=0.0006), delayed decline in vital capacity<20% (p=0.0088), later start of non-invasive ventilation (p = 0.0006), tracheotomy (p=0.0040) and arthrodesis (p<0.0001). Conversely, residual dystrophin did not influence the age of occurrence of LVEF<30% (p=0.2172). In conclusion, very low residual dystrophin expression is sufficient to shift the natural history of dystrophinopathy towards the milder Becker phenotype. These data suggest that restoration of low dystrophin levels might be sufficient to achieve long-term clinical benefit from novel therapeutic strategies. Results will be discussed in the light of the limited number of study subjects, time of observation and employed Western Blot methodology.
Fichier non déposé

Dates et versions

hal-04015244 , version 1 (05-03-2023)

Identifiants

  • HAL Id : hal-04015244 , version 1

Citer

Yvan De Feraudy, Rabah Ben Yaou, Karim Wahbi, France Leturcq, Helge Amthor, et al.. Residual very low dystrophin levels mitigate dystrophinopathy towards Becker muscular dystrophy. 25th International Annual Congress of the World-Muscle-Society (WMS), Oct 2018, Mendoza (Argentina), Argentina. ⟨hal-04015244⟩
17 Consultations
0 Téléchargements

Partager

Gmail Mastodon Facebook X LinkedIn More