Duchenne muscular dystrophy: Evolving therapeutic strategies and multidimensional evaluation approaches

Abstract

Duchenne muscular dystrophy (DMD) is a severe X-linked muscular disorder caused by the absence of dystrophin. Standard therapies prolong survival; however, there is an increasing need for disease-modifying approaches and sensitive evaluation tools. This review presents a summary of the recent advances in DMD therapeutic strategies and multidimensional evaluation approaches, emphasizing their clinical applicability and future perspectives. In this study, a comprehensive review of the current literature was conducted focusing on mutation-specific therapies (exon skipping and gene therapy), non-mutation-specific pharmacological interventions (steroids, vamorolone, and histone deacetylase inhibitors), and emerging modalities such as cell-based therapy. The clinical outcome measures used across the disease stages were also examined, ranging from functional motor tests and imaging biomarkers to digital endpoints and quality of life (QOL) indices. Exon skipping and microdystrophin gene therapies have shown promising results in restoring partial dystrophin expression. Vamorolones and givinostat are alternative drugs with improved safety profiles. Time-based motor tests (such as time to sand, 10 m run) and digital biomarkers (Stride Velocity 95th Centile) enable the earlier detection of disease progression. Natural history data, including large registry-based datasets, enhance the interpretation of clinical trials. Patient-reported outcomes and disease-specific QOL measures, such as the DMD-QoL, are increasingly being incorporated to assess meaningful treatment benefits. The therapeutic landscape of DMD is evolving toward combination and personalized approaches. Multidimensional stage-specific evaluations are essential to capture functional changes and their therapeutic effects. Ongoing research on gene-, pharmacological-, and cell-based therapies, coupled with robust outcome assessments, may further improve patient care and QOL.