OCU400 (NR2E3-AAV) is a novel gene therapy with the potential to be broadly effective in restoring retinal integrity and function across a range of genetically diverse inherited degenerative retinal diseases (IRDs).
It consists of a functional copy of the 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, stabilizing cells and potentially rescuing photoreceptor degeneration.
Unlike single-gene replacement approaches, which have shown tremendous promise in rare retinal diseases despite being highly specific for a single condition, OCU400 represents a powerful and remarkably broadened means of treating a variety of IRDs with a single therapy.
In mouse models, treatment with the NR2E3 gene effectively prevented the development of multiple genetically diverse inherited retinal diseases by protecting photoreceptors from further damage after disease onset. Ocugen is advancing OCU400 in an effort to create vision-sparing therapies for rare/orphan IRDs such as NR2E3 mutation associated recessive retinal degeneration, Leber Congenital Amaurosis (LCA), Bardet-Biedl Syndrome (BBS) and Rhodopsin mutations associated retinitis pigmentosa and other retinal degenerations.
Currently, Ocugen is developing OCU400 as a gene augmentation therapy product for the treatment of NR2E3 mutation associated recessive retinal degenerative diseases. In a mouse model of NR2E3 mutation, NR2E3 delivery to retinal cells reversed disease progression and restored retinal histology. Based on these encouraging results, Ocugen plans to initiate a Phase 1/2a clinical study by 2020.
About Inherited Retinal Diseases
Many degenerative retinal conditions are caused by genetic mutations that are passed down within families and lead to progressive disease, severe visual impairment and blindness. Unfortunately, there are a multitude of known mutations in multiple different genes that cause a variety of IRDs. Treating these conditions has been a significant challenge due to the sheer volume of potential therapeutic targets. Gene replacement therapy is a promising approach to providing lasting restoration of normal retinal function, but such therapies can only address one gene at a time, limiting their effectiveness. OCU400 is designed to modify the expression of key networks of genes involved in maintaining retinal homeostasis, potentially compensating for the impairment caused by the original gene mutation.
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