OCU400 (AAV-NR2E3) is a novel gene therapy product candidate with the potential to be broadly effective in restoring retinal integrity and function across a range of genetically diverse inherited retinal diseases (“IRDs”). It consists of a functional copy of a nuclear hormone receptor (“NHR”) gene, NR2E3, delivered to target cells in the retina using an adeno-associated viral (“AAV”) vector. As a potent modifier gene, expression of NR2E3 within the retina may help reset retinal homeostasis, potentially stabilizing cells and rescuing photoreceptor degeneration.
In five unique mouse models of Retinitis Pigmentosa (RP), treatment with the AAV-NR2E3 gene by subretinal injection rescued multiple genetically diverse IRDs by protecting photoreceptors from further damage after disease onset. The five RP models tested were rd1 (PDE6β associated RP), Rho-/- and RhoP23H (both Rhodopsin associated RP), rd16 (Leber Congenital Amaurosis) and rd7 (Enhanced S-cone Syndrome). The study, published in Nature Gene Therapy, demonstrates the potential of a novel modifier gene therapy to elicit broad-spectrum therapeutic benefits in early and intermediate stages of RP and Leber Congenital Amaurosis (LCA) based on animal models, showing the potential for a mutation-agnostic treatment.
Currently, Ocugen is developing OCU400 for the treatment of multiple IRDs encompassing RP and LCA.
Learn more about our gene therapy platform
- Li, S., Datta, S., Brabbit, E. et al. Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa. Gene Ther (2020).
- Haider, N. B. et al. Mapping of genetic modifiers of Nr2e3rd7/rd7 that suppress retinal degeneration and restore blue cone cells to normal quantity. Mammalian Genome 19, 145-154, 2008.
- Olivares, A. M. & Haider, N. B. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases. 9, 93-121, (2015).
- Cheng, H. et al. In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development. Hum Mol Genet 15, 2588-2602, (2006).
- Haider, N. B. et al. The transcription factor Nr2e3 functions in retinal progenitors to suppress cone cell generation. Visual Neuroscience 23, 917-929, (2006).
- Schorderet, D. F. & Escher, P. NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP). Human Mutation 30, 1475-1485, (2009).
OCU410 (AAV-RORA) is a modifier gene therapy product candidate being developed for the treatment of dry age-related macular degeneration (Dry AMD). OCU410 utilizes an AAV delivery platform for the retinal delivery of the RORA (RAR Related Orphan Receptor A) gene. Various genes associated with AMD are regulated by RORA. The RORA protein plays an important role in lipid metabolism and demonstrates an anti-inflammatory role, which we believe could be a potential therapeutic candidate for dry AMD based on in-vitro and in-vivo (animal model) studies.
Using the same technology as OCU410, Ocugen plans to submit an IND for Stargardt disease, an orphan eye disease, in Q2 2023.