Leigh F, Ferlini A, Biggar D, Bushby K, Finkel R, Morgenroth LP, Wagner KR
Duchenne muscular dystrophy is the most common form of childhood muscular dystrophy. A mutation in the DMD gene disrupts dystrophin (protein) production, causing damage to muscle integrity, weakness, loss of ambulation, and cardiopulmonary compromise by the second decade of life. Life expectancy has improved from mid-teenage years to mid-20s with the use of glucocorticoids and beyond the third decade with ventilator support and multidisciplinary care. However, Duchenne muscular dystrophy is associated with comorbidities and is a fatal disease.
Glucocorticoids prolong ambulation, but their side effects are significant. Emerging investigational therapies have surfaced over the past decade and have rapidly been tested in clinical trials. Gene-specific strategies include nonsense readthrough, exon skipping, gene editing, utrophin modulation, and gene replacement. Other mechanisms include muscle regeneration, antioxidants, and antifibrosis and anti-inflammatory pathways. With potential therapies emerging, early diagnosis is needed to initiate treatment early enough to minimize morbidity and mortality. Newborn screening can be used to significantly improve early diagnosis, especially for gene-specific therapeutics.
Harvard University, USA; Seattle Children's Hospital, USA; University of Ferrara, Italy; Holland Bloorview Kids Rehabilitation Hospital, Canada; John Walton Centre for Muscular Dystrophy Research, UK; Nemours Children's Health System, USA; Children's National Health System, USA; Kennedy Krieger Institute, USA; Johns Hopkins University, USA
10.1542/peds.2018-0333C read more
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