Emerging gene therapies in the treatment of recessive dystrophic epidermolysis bullosa: a systematic review.

Abstract

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a life-limiting collagen type VII alpha-1 (COL7A1)-related disorder characterized by skin fragility, chronic wounds, and early mortality. Gene therapies aim to restore collagen type VII (C7) expression and improve wound healing, but clinical evidence remains limited.

Objective: To synthesize current evidence on the safety and effectiveness of gene therapy approaches for RDEB.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched major databases through 7 March 2025 for interventional studies evaluating gene therapies in RDEB. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Given the substantial heterogeneity, findings were synthesized narratively without meta-analysis.

Results: Five clinical trials met the inclusion criteria and evaluated ex vivo autologous cell-based therapies and in vivo topical vector delivery. Topical herpes simplex virus type 1-based COL7A1 therapy achieved a significantly higher rate of complete wound closure than controls (71% versus 20% at 3 months; P < 0.001). Ex vivo epithelial grafting demonstrated durable clinical benefit during long-term follow-up. Molecular analyses generally showed restoration or increased C7 expression. Patient-reported outcomes improved alongside sustained wound healing. Treatments were generally well tolerated, with predominantly mild adverse events, no treatment-related serious safety signals, and evidence of immunologic tolerance to recombinant C7.

Conclusion: Gene therapy for RDEB demonstrates a favorable early safety profile and promising efficacy. However, the small number of heterogeneous early-phase trials and limited follow-up preclude definitive conclusions. Larger, rigorously designed studies with extended follow-up are required to confirm long-term safety and clinical effectiveness.