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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Modifier gene therapy rescues retinal degeneration in mice

Ocugen has published preclinical data supporting the therapeutic potential of a genetic modifier gene therapy in treating multiple forms of retinitis pigmentosa (RP).

RP is a group of inherited retinal degenerative diseases characterized by progressive degeneration of rod and cone photoreceptors, resulting in vision loss. With a prevalence of approximately 1 in 3500, it is one of the most common visual impairments worldwide and currently there is no treatment available. Over 150 unique gene mutations have been associated with RP, making it highly heterogenic, with high variability in disease onset, severity, and progression.

The findings published in Nature Gene Therapy highlights the nuclear hormone receptor gene NR2E3 as a genetic modifier and therapeutic agent to treat multiple retinal degenerative diseases. Ocugen’s investigational gene therapy product OCU400 uses a functional copy of NR2E3 and is designed to target retinal cells using an AAV vector.

The study was conducted in five independent RP mouse models and efficacy data demonstrated that subretinal administration of OCU400 could rescue all the five animal models by resetting retinal homeostasis. As a potent modifier gene, expression of NR2E3 within the retina is therefore thought to help reset retinal homeostasis, stabilize cells and potentially rescue photoreceptors from degeneration.

Given the role of NR2E3 in modulating numerous key biological networks essential for maintaining retinal homeostasis, this gene therapy is thought to have the potential in eliciting broad-spectrum therapeutic benefits in early and intermediate stages of RP.

The platform was developed by Dr Neena Haider, Associate Professor of Ophthalmology at Harvard Medical School and Associate Scientist at the Schepens Eye Research Institute (SERI) of Massachusetts Eye and Ear. Ocugen obtained an exclusive worldwide license from SERI to develop and commercialize ophthalmology products based on the platform.

OCU400 (NR2E3-AAV) has received two orphan drug designations targeting two distinct inherited retinal diseases (IRDs): NR2E3 mutation-associated retinal diseases and CEP290 mutation-associated retinal diseases.

Dr Rasappa Arumugham, Ocugen’s CSO commented: “One of the biggest advantages of our modifier gene therapy platform is that it has the potential to eliminate the need for individual gene replacement and gene editing strategies and may revolutionize gene therapy treatments for eye diseases. Inherited retinal degenerations such as RP affect over 1.5 million people worldwide. Over 150 gene mutations have been associated with RP and this number represents only 60% of the RP population. The remaining 40% of RP patients cannot be genetically diagnosed, making it difficult to develop individual treatments. Our modifier gene therapy has potential to eliminate the need for developing more than 150 individual products and provide one treatment option for all RP patients. We are completing preclinical studies for OCU400 and anticipate commencing a Phase 1/2a clinical trial in patients in 2021.”

Source: Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa; Li S et al., Nature Gene Therapy, March 2020. DOI

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