Recent progress in emerging therapeutics and evaluation of oculopharyngeal muscular dystrophy.

PURPOSE OF REVIEW: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, genetic, neuromuscular disorder causing progressive ptosis, dysphagia and proximal muscle weakness. This review highlights emerging therapeutic strategies and recent advances in understanding the clinical phenotypes, genetic mechanisms and pathophysiology of OPMD. RECENT FINDINGS: OPMD results from a short polyalanine expansion in the nuclear polyadenosine-binding protein 1 (PABPN1) gene. Current treatment is primarily surgical to alleviate ptosis and dysphagia; however, no disease-modifying therapy is currently available. Emerging therapeutic approaches focus on reducing intranuclear inclusions containing aggregates of expanded PABPN1, a characteristic pathological feature of muscle biopsies in OPMD. Another promising strategy uses gene therapy to suppress mutant PABPN1 expression while increasing expression of the wild-type protein. Advancing OPMD therapies will require coordinated trial-readiness resources - including natural history data, validated outcome measures and biomarkers, patient registries, epidemiological and health-economic evidence, and patient-association engagement - to support efficient clinical development, reimbursement, and equitable access. SUMMARY: Care for OPMD patients currently remains primarily supportive. However, advances in the genetic understanding of OPMD and in gene therapy have led to promising potential treatment approaches providing hope for future disease-modifying therapies.