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Overview of Gene Therapy in Spinal Muscular Atrophy and Duchenne Muscular Dystrophy
  • Nicolas Abreu,
  • Megan Waldrop
Nicolas Abreu
Nationwide Children's Hospital

Corresponding Author:[email protected]

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Megan Waldrop
Nationwide Children's Hospital
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Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec-xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre-mRNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD.
30 Jun 2020Submitted to Pediatric Pulmonology
01 Jul 2020Submission Checks Completed
01 Jul 2020Assigned to Editor
02 Jul 2020Reviewer(s) Assigned
03 Aug 2020Review(s) Completed, Editorial Evaluation Pending
03 Aug 2020Editorial Decision: Revise Minor
25 Aug 20201st Revision Received
25 Aug 2020Submission Checks Completed
25 Aug 2020Assigned to Editor
25 Aug 2020Reviewer(s) Assigned
27 Aug 2020Review(s) Completed, Editorial Evaluation Pending
27 Aug 2020Editorial Decision: Accept
14 Sep 2020Published in Pediatric Pulmonology. 10.1002/ppul.25055