Abstract: Retinitis pigmentosa (RP), diabetic retinopathy (DR), age-related macular degeneration (AMD), and Stargardt's disease are serious eye diseases which lead to to irreversible photoreceptor loss and incurable blindness. RP affects over 2 million people worldwide, with less than 5% of cases which has Rpe65 mutation, benefitting from gene therapy. DR impacts 93 million individuals globally and can be slowed by treatments such as anti-VEGFs and laser therapies, though late-stage DR remains incurable. AMD affects nearly 200 million elderly people worldwide, leading to blindness in its late stages. Stargardt's disease, the most common inherited juvenile macular degeneration, affects 1 in 8,000 to 10,000 people, with no available treatments to slow its progression.
In recent regenerative therapy efforts, ReNeuron and jCyte have conducted phase 2 clinical trials using retinal progenitor cells (RPCs) derived from fetal retina to treat RP patients. The transplanted cells showed efficacy in rescuing patients' vision for at least one year. However, ReNeuron halted further trials due to surgical complications, while jCyte plans to proceed with a US pivotal trial, emphasizing that visual function restoration depends on patients' central visual field at baseline. The use of human retinal progenitor cells (hRPCs) derived from fetal tissue is limited by availability and ethical concerns. Additionally, differentiating human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) into RPCs is time-consuming, labor-intensive, and yields low efficiency.
To address the unmet medical need for photoreceptor degeneration, this study aims to generate retinal progenitor-like cells through chemical-based direct reprogramming without genome manipulation of exogenous transcription factors. Our data indicate that these chemical-induced retinal progenitor-like cells can be efficiently and safely produced in just 5 days and potentially aid in the recovery of visual function in blind animal models. More than 90% of the conversion cells show electrophysiology activity by calcium image. These encouraging results suggest that chemical-induced retinal progenitor-like cells have high clinical potential. We are progressing through preclinical tests and preparing to start clinical trials.
