Dystrophic epidermolysis bullosa (DEB) is caused by mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils. Loss of anchoring fibrils results in sublamina densa cleavage with scarring blisters, mucosal involvement, severe morbidity in recessive forms (RDEB), and aggressive cutaneous squamous cell carcinoma (cSCC) by middle adulthood. Until 2023, treatment was purely supportive (wound care, nutrition, infection control).
Beremagene geperpavec (B-VEC, Vyjuvek) is a non-replicating, non-integrating herpes simplex virus type-1 (HSV-1) vector encoding two copies of COL7A1, applied as a topical gel weekly to chronic wounds. Phase 3 GEM-3 trial showed 67% wound closure at 6 months versus 22% with placebo. FDA approval came in May 2023 for patients aged 6 months and older with mutations in COL7A1, marking the first topical gene therapy. It does not require systemic immunosuppression, can be administered at home (after training), and treatment is continued as long as wounds persist.
Other emerging modalities: dabocemagene autoficel (D-Fi/PTR-101) involves autologous fibroblasts genetically corrected with lentiviral COL7A1 ex vivo, then injected into wounds. Allogeneic mesenchymal stromal cell infusions reduce inflammation and may transiently produce COL7. Allogeneic hematopoietic stem cell transplantation (HSCT) has been performed in severe RDEB with mixed results (significant transplant-related mortality). Gentamicin (intravenous or topical) can induce read-through of premature termination codons in 10-25% of RDEB patients with nonsense mutations, partially restoring COL7. Aminoglycoside-modified compounds and small-molecule read-through agents are in development. CRISPR-Cas9 and base editing strategies for COL7A1 correction are in preclinical and early clinical evaluation. Comprehensive multidisciplinary care remains the foundation: meticulous wound care, infection prevention, nutritional optimization, anemia and growth management, esophageal dilation for strictures, hand contracture surgery, pain management, and annual whole-body skin examination starting in late adolescence for cSCC surveillance (cumulative lifetime risk approaches 90% by age 55 in severe RDEB).