Towards a Cure: Emerging Therapeutic Advances for DMD, LGMD, and GNEM- Insights from Pre-Clinical and Clinical Research

Duchenne muscular dystrophy (DMD), Limb-girdle muscular dystrophies (LGMD), and GNE myopathy (GNEM) are progressive neuromuscular rare genetic diseases with differing etiologies either due to defects in structural muscle proteins or impaired metabolism and manifests through progressive weakening and deterioration of skeletal muscle tissues. This review summarizes current and recent clinical trials worldwide, highlighting curative approaches for neuromuscular diseases such as DMD, LGMD, and GNEM. We compiled and summarized latest and most promising outcomes from ongoing global clinical trials, using information from official websites, news sources, trial registries, databases and literature across four key therapeutic modalities: 1) palliative therapies: steroidal and non-steroidal 2) gene therapy and gene-targeted interventions, 3) cell-based regenerative strategies and 4) universal treatments (therapies not limited to the mutation type). We also highlighted the risks associated with gene therapy and discussed key regulatory considerations.Several current clinical trials show promise for muscular dystrophy treatments. RGX-202 gene therapy demonstrates early muscle strength improvement in DMD children. MyoPAXon, a stem cell therapy for DMD muscle regeneration, has FDA clearance to begin trials. Sevasemten (EDG-5506) trials report slowed DMD/BMD progression. SRP-9003 gene therapy targets protein restoration in LGMD. ACENOBEL, approved in Japan for GNEM, may delay disease progression if started early. These trials offer high potential to become widely available treatments improving quality of life and provide life-saving therapeutic options. Additionally, Indian specific founder mutations for the mentioned muscular dystrophies are highlighted to understand the disease etiology in Indian populations for precise diagnostics and therapeutics.