Gene Therapies for Spinal Muscular Atrophy and Duchenne Muscular Dystrophy: A Pathbreaking Moment in Therapeutics
. Salwa
Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
Safia Fathima Anver Pasha
Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
Wafeeqa x Wafeeqa Fatima
Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
Suresh Kumar Srinivasamurthy *
Department of Pharmacology, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
*Author to whom correspondence should be addressed.
Abstract
Background: Gene therapy has proved to be a boon for neuromuscular diseases. A concept introduced in the early 1960’s, has been put into clinical practice in the past 5-10 years. The process by which a healthy gene replaces a defective gene in a human body through vectors is truly pathbreaking. Patients with inherited degenerative neuromuscular disorders such as spinal muscular atrophy, and muscular dystrophies undergo progressive deterioration and eventually death. Gene therapy and other adjunctive clinical approaches have provided such patients with a second chance to truly live their life. This review is centered on the different gene therapies currently developed for spinal muscular atrophy and Duchenne muscular dystrophy and also sheds light on the emerging therapies.
Methods: Literature search was done in Medline, Embase, and Google Scholar. The relevant and important articles were included for developing the narrative review.
Results and Discussion: The nusinersen, risdiplam, zolgensma, eteplirsen, golodirsen, viltolarsen, casimersen and ataluren are developed as gene therapies for Spinal muscular atrophy and Duchenne muscular dystrophy. The therapies approved under orphan drug designation have shown muscle strength improvement in clinical trials. However, long-term data on safety and efficacy is to be determined. The cost of the therapies acts as an impediment in most cases.
Conclusion: The development of gene therapies for inherited genetic disorders would be a prelude for several other genetic diseases. The studies in this arena would provide a prototype for translational research from bench to bedside. Further efforts are mandated towards long term safety, efficacy, and affordability of therapies.
Keywords: Gene therapy, spinal muscular atrophy, muscular dystrophies, SMN-1 gene, gene splicing, viral vectors, dystrophin gene, Adeno-Associated Virus (AAV)-9 vectors, antisense oligonucleotides (ASOs), exon skipping, CRISPR-Cas9