GUCY2D
Retinal guanylate cyclase 1 (RetGC1/GC-E); a key enzyme in the phototransduction cascade that synthesizes cGMP in photoreceptor outer segments. Essential for both rod and cone function. Regulated by GCAPs (guanylate cyclase-activating proteins) in a calcium-dependent manner. First LCA gene locus mapped (1995) and gene identified (Perrault et al. 1996).
Active Clinical Trials
ATSN-101 (Atsena/Nippon Shinyaku) — Phase 1/2 completed with 15 patients, clinically meaningful improvements at highest dose (Lancet 2024). Phase 3 global pivotal trial planned. Nippon Shinyaku exclusive U.S./Japan rights (Nov 2024). FDA RMAT + Orphan Drug + Rare Pediatric Disease designations. Founded by Shannon Boye (CSO) at Atsena Therapeutics, based on UF preclinical work (2010).
17p13.1
Autosomal Recessive
10-20% of LCA cases
Key Clinical Features
- 1Early profound vision loss — but with remarkably preserved retinal structure
- 2Significant photophobia (light sensitivity)
- 3Lack of color perception
- 4Substantial residual rod-driven vision in some patients
- 5Well-preserved macular anatomy on OCT — wide therapeutic window for gene therapy
- 6Preserved postretinal pathways (optic nerve, visual cortex remain viable)
- 7Hyperopia common
- 8Residual cone vision correlates with biochemical activity of specific mutant alleles
Clinical Trials
ATSN-101 Gene Therapy for GUCY2D-LCA1 (Phase 1/2)
Atsena Therapeutics · Phase 1/2
Sources:
- OMIM 204000
- Nature Genetics - Perrault et al. 1996 (Discovery)
- J Neurosci - GC1 Knockout Mouse (1999)
- PLoS ONE - First Gene Therapy in Mice (2010)
- Hum Mol Genet - Cone Vision Correlates (2013)
- CSH Perspectives - LCA1 Review (2015)
- Am J Ophthalmol - Trial Outcomes (2017)
- Retina - Natural History Study (2019)
- The Lancet - ATSN-101 Results (2024)
- FFB - Nippon Shinyaku Deal (2024)