LCA5 (Lebercilin)
Lebercilin; involved in ciliary transport in photoreceptors
Active Clinical Trials
Opus Genetics OPGx-LCA5 (OPGx-001) Phase 1/2 (NCT05616793) at UPenn — subretinal AAV8 carrying human LCA5 cDNA. One-year adult results showed recovery of cone-mediated vision (~1 log unit; Aleman et al., Mol Ther 2025), and an adolescent cohort showed similar early gains with good tolerability (ARVO 2026). In July 2026, after a Type B Rare Disease Evidence Principles (RDEP) meeting, the FDA aligned on a streamlined Phase 3 registrational design: eight participants each serve as their own natural-history control after a six-month run-in before bilateral treatment, with a primary endpoint of a mean gain of at least 7 dB in retinal sensitivity across 16 central loci (microperimetry; ~10.5 dB was seen in Phase 1/2). A BLA may be filed on six-month efficacy data, with 12-month durability provided during review; the program holds Orphan Drug, Rare Pediatric Disease, and RMAT designations. Dosing anticipated Q4 2026.
Sourced & cited — not yet expert-reviewed
Every statement here is backed by a cited primary source, but a specialist has not formally reviewed this page yet.
6q14.1
Autosomal Recessive
1-2% of LCA cases
Key Clinical Features
- 1Ciliopathy
- 2Early-onset severe vision loss
- 3Rapid, severe photoreceptor degeneration from early childhood, with relative central (foveal) cone sparing that persists over a decades-long course (natural-history data, ARVO 2026)
Clinical Trials
OPGx-LCA5 Gene Therapy for Lebercilin-LCA5
Opus Genetics · Phase 1/2
Sources:
- OMIM 604537
- Opus Genetics - OPGx-LCA5
- Mol Ther 2025 - OPGx-001 One-Year Phase 1/2 Results (Aleman et al.)
- IOVS/ARVO 2026 - OPGx-001 Pediatric Cohort (abstract)
- IOVS/ARVO 2026 - LCA5 Natural History (abstract)
- Opus Genetics - FDA alignment on Phase 3 registrational design (Jul 2026)
- Clinical Leader - How FDA alignment shapes OPGx-LCA5 strategy (2026)