AIPL1
Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1); a specialized chaperone protein essential for assembly and stability of PDE6 (phosphodiesterase 6) holoenzyme in photoreceptors. Contains FKBP-like and TPR domains. Interacts with HSP90 and NUB1. Required for both rod and cone photoreceptor survival. First identified in 2000 by Sohocki et al.
Active Clinical Trials
MeiraGTx rAAV8.hRKp.AIPL1 — First-in-human results (Lancet 2025): all 11 children aged 1-4 gained visual acuity with no serious adverse effects. Preclinical proof-of-concept in knockout mice (Tan/Ali, JCI 2009). Eli Lilly collaboration for global commercialization ($75M upfront, up to $475M). MAA/BLA submission planned.
17p13.2
Autosomal Recessive
1-2% of LCA cases
Key Clinical Features
- 1Early profound vision loss — one of the most severe LCA subtypes
- 2Rapid photoreceptor degeneration from birth due to PDE6 loss
- 3Relative preservation of outer retina before age 4 (narrow therapeutic window)
- 4Progressive total macular atrophy
- 5Both rod and cone function severely affected from infancy
- 6AIPL1 functions as a PDE6 chaperone — loss of AIPL1 leads to near-complete PDE6 degradation
- 7Gene therapy must be delivered very early (ages 1-4) to be effective
Clinical Trials
AIPL1 Gene Therapy First-in-Human Study
MeiraGTx / UCL / GOSH · Phase 1/2
LX107 AIPL1 Gene Therapy (Eli Lilly)
Eli Lilly · TBD