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Research paper
The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials
  1. Valeria Ricotti1,3,
  2. Deborah A Ridout2,3,
  3. Marika Pane4,
  4. Marion Main1,3,
  5. Anna Mayhew5,
  6. Eugenio Mercuri1,4,
  7. Adnan Y Manzur1,3,
  8. Francesco Muntoni1,3
  9. on behalf of UK NorthStar Clinical Network
    1. 1Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK
    2. 2Department of Population, Policy and Practice Programme, UCL Institute of Child Health, London, UK
    3. 3Great Ormond Street Hospital, London, UK
    4. 4Department of Paediatric Neurology, Catholic University, Rome, Italy
    5. 5Institute of Human Genetics, Newcastle, UK
    1. Correspondence to Professor Francesco Muntoni, Dubowitz Neuromuscular Centre, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; f.muntoni{at}ucl.ac.uk

    Abstract

    Objective With 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.

    Methods Through 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.

    Results On 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.

    Conclusions Our study provides a novel insight on the current natural history of DMD, which will be instrumental for the design of future clinical trials.

    • NEUROMUSCULAR
    • MUSCULAR DYSTROPHY

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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