Lessons Learned From Translational Research in Neuromuscular Diseases: Impact on Study Design, Outcome Measures and Managing Expectation

Georgia Stimpson; Mary Chesshyre; Giovanni Baranello; Francesco Muntoni

doi:10.3389/fgene.2021.759994

Lessons Learned From Translational Research in Neuromuscular Diseases: Impact on Study Design, Outcome Measures and Managing Expectation

Front Genet. 2021 Dec 7:12:759994. doi: 10.3389/fgene.2021.759994. eCollection 2021.

Authors

Georgia Stimpson¹, Mary Chesshyre^{1

2}, Giovanni Baranello^{1

2}, Francesco Muntoni^{1

2}

Affiliations

¹ Developmental Neuroscience Research and Training Department, Dubowitz Neuromuscular Centre, Faculty of Population Health Sciences, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
² NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.

Abstract

Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD), two of the most common, child onset, rare neuromuscular disorders, present a case study for the translation of preclinical research into clinical work. Over the past decade, well-designed clinical trials and innovative methods have led to the approval of several novel therapies for SMA and DMD, with many more in the pipeline. This review discusses several features that must be considered during trial design for neuromuscular diseases, as well as other rare diseases, to maximise the possibility of trial success using historic examples. These features include well-defined inclusion criteria, matching criteria, alternatives to placebo-controlled trials and the selection of trial endpoints. These features will be particularly important in the coming years as the investigation into innovative therapy approaches for neuromuscular diseases continues.

Keywords: duchenne and becker muscular dystrophy; inclusion criteria; matching criteria; spinal muscular atrophy; translational research; trial design.

Publication types

Review

Grants and funding

GB and GS are supported by a grant from the Great Ormond Street Hospital Children's Charity and Muscular Dystrophy UK. FM and MC are supported by the NIHR Great Ormond Street Biomedical Research Centre. The views expressed are those of the author(s) and are not necessarily those of the NHS, the NIHR or the Department of Health.