North Star Ambulatory Assessment changes in ambulant Duchenne boys amenable to skip exons 44, 45, 51, and 53: A 3 year follow up

PLoS One. 2021 Jun 25;16(6):e0253882. doi: 10.1371/journal.pone.0253882. eCollection 2021.

Abstract

Introduction: The aim of this study was to report 36-month longitudinal changes using the North Star Ambulatory Assessment (NSAA) in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53.

Materials and methods: We included 101 patients, 34 had deletions amenable to skip exon 44, 25 exon 45, 19 exon 51, and 28 exon 53, not recruited in any ongoing clinical trials. Five patients were counted to skip exon 51 and 53 since they had a single deletion of exon 52.

Results: The difference between subgroups (skip 44, 45, 51 and 53) was significant at 12 (p = 0.043), 24 (p = 0.005) and 36 months (p≤0.001).

Discussion: Mutations amenable to skip exons 53 and 51 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had higher scores both at baseline and at follow up.

Conclusion: Our results confirm different progression of disease in subgroups of patients with deletions amenable to skip different exons. This information is relevant as current long term clinical trials are using the NSAA in these subgroups of mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Disease Progression
  • Dystrophin / genetics*
  • Exons / genetics
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Men
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / pathology
  • Mutation / genetics*
  • Severity of Illness Index
  • Walking / physiology

Substances

  • Dystrophin

Grant support

The study was partially founded by the Italian Telethon (GUP 15011) to EM and partially funded by the Association Française contre les Myopathies (AFM) for the collection and analysis of the data from the patients recruited in iMDEX natural history study (IMDEX/ NCT02780492). We are grateful for the support of the UCL MRC Neuromuscular Biobank and the Muscular Dystrophy UK for the support given to the Dubowitz Neuromuscular Centre. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. FM and TV are supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, London. VS is supported by the NIHR Newcastle BRC. Several members of the iMDEX consortium and of the International DMD group are members of the European Reference Network for Neuromuscular Diseases (EURO-NMD). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.