Background:
Duchenne muscular dystrophy (DMD) is a severe genetic disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration. Translational research bridges preclinical discoveries and clinical applications, driving the development of novel therapies. Evaluating the effectiveness of this process is essential to guide future advancements.
Objectives:
This meta-analysis assesses the impact of translational research on DMD, focusing on preclinical model efficacy, correlation with clinical outcomes, and success rates of therapies advancing to clinical trials.
Methods:
A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov identified preclinical and translational studies published up to 2024. Eligible studies included those on gene-based, pharmacological, and cell-based therapies. Data were synthesized following PRISMA guidelines, with outcomes analyzed for dystrophin restoration, functional improvements, and clinical translation.
Results:
Forty-five studies (30 preclinical and 15 clinical) were analyzed. Preclinical models, particularly mdx mice, demonstrated dystrophin restoration of 30%–50% and muscle strength improvements of 45% (95% CI: 38%–52%, p < 0.001). Clinical trials reported dystrophin restoration of 5%–15% and functional gains, including a 28-meter increase in the 6-minute walk test (95% CI: 20–36, p < 0.01). Gene therapies and exon skipping emerged as leading strategies with strong translational potential. Limitations included variability in preclinical model predictability and challenges in scaling to human applications. Subgroup analyses highlighted better outcomes with humanized models and biomarker use.
Conclusion:
Translational research has driven significant progress in DMD therapy development, particularly in gene and exon skipping therapies. Addressing preclinical model limitations and scalability challenges is essential to enhance the efficiency of bench-to-bedside translation and improve therapeutic outcomes for DMD patients.