The Role of Antisense Oligonucleotides in Duchenne Muscular Dystrophy: A Comprehensive Meta-Analysis

Topic:

Other

Poster Number: V401

Author(s):

Mahmoud M. Elsayed, MD, MME Foundation, Ahmed Abouzeid, Newgiza University, Monia Medhat, Newgiza University, Farah Abdelrahman, Newgiza University, Salma Elsenbawy, Newgiza University, Nahed Ali, BA, MME Foundation, Moatazbellah Mustafa, Newgiza University, Mohamed Abouzaid, Newgiza University

Background:
Duchenne muscular dystrophy (DMD) is a severe X-linked disorder caused by mutations in the DMD gene, leading to dystrophin deficiency and progressive muscle degeneration. Antisense oligonucleotides (AONs) are a promising therapeutic strategy that induces exon skipping to restore the DMD reading frame, enabling production of functional dystrophin. Despite encouraging results, variability in outcomes highlights the need for comprehensive evaluation.

Objectives:
This meta-analysis examines the efficacy and safety of AON therapies in DMD, focusing on dystrophin restoration, functional improvements, and key factors influencing therapeutic outcomes.

Methods:
A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov identified preclinical and clinical studies published up to 2024. Eligible studies assessed AON therapies targeting exons 44, 45, or 51. Data were synthesized following PRISMA guidelines, and study quality was evaluated using risk of bias tools.

Results:
Thirty-five studies (20 preclinical and 15 clinical trials) were included. Preclinical models showed dystrophin restoration levels of 30%–45% of normal, with significant improvements in muscle strength (mean increase: 40%, 95% CI: 32%–48%, p < 0.001). Clinical trials demonstrated dystrophin restoration levels of 5%–15%, accompanied by functional gains in the 6-minute walk test (mean increase: 25 meters, 95% CI: 15–35 meters, p < 0.01). Safety profiles were favorable, with common adverse events including mild injection site reactions and transient creatine kinase elevations. Subgroup analyses indicated improved outcomes with early treatment and optimized dosing. Conclusion: AON therapies offer significant potential for treating DMD, achieving meaningful dystrophin restoration and functional improvements with manageable safety concerns. Further refinement of AON chemistries and delivery systems is essential to maximize therapeutic impact. These findings reinforce the role of AONs as a key pillar in the evolving landscape of DMD therapy.