Genetic-Based Treatment Strategies for Muscular Dystrophy and Congenital Myopathies. Issue 6 (December 2022)

• Record Type: Journal Article
• Authors: Findlay, Andrew R.; Weihl, Conrad C.
• Other Names: Hehir Michael K. guest-editor.
• Is Part Of: Continuum. Volume 28:Issue 6(2022)
• Page Start: 1800
• Page End: 1816
• Publication Date: 2022-12
• Subjects: Neurology -- Periodicals; Neurology -- Study guides -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1212/CON.0000000000001203
• Languages: English
• ISSNs: 1080-2371

Abstract

ABSTRACT: PURPOSE OF REVIEW: This article discusses the foundational concepts of genetic treatment strategies employed in neuromuscular medicine, as well as the importance of genetic testing as a requirement for applying gene-based therapy. RECENT FINDINGS: Gene therapies have become a reality for several neuromuscular disorders. Exon-skipping and (in Europe) ribosomal read-through approaches are currently available to a subset of patients with Duchenne muscular dystrophy. Microdystrophin gene replacement has shown promise and is nearing the final stages of clinical trials. Numerous gene-based therapies for other muscular dystrophies and congenital myopathies are progressing toward approval as well. SUMMARY: Muscular dystrophies and congenital myopathies are a heterogenous group of hereditary muscle disorders. Confirming a diagnosis with genetic testing is not only critical for guiding management, but also an actual prerequisite for current and future gene therapies. Recessive loss-of-function or dominant haploinsufficiency disorders may be treated with gene replacement strategies, whereas dominant negative and toxic gain-of-function disorders are best addressed with a variety of knockdown approaches. It is important to recognize that many therapeutics are mutation specific and will only benefit a subset of individuals with a specific disease.