Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration

Many modalities are being evaluated for the treatment of retinal degenerative diseases such as retinitis pigmentosa (RP), including stem cell therapy where dead or damaged cells are replaced by healthy ones. In a previous study, subretinal injections of human neural progenitor cells (hNPCs) and an engineered version that expresses a nerve growth factor (hNPCGDNF) successfully preserved visual function. However, these experiments were performed using mouse models showing early stages of retinal degeneration and did not translate to clinical patients in later stages of the disease.

In this study, two groups of Royal College of Surgeon (RCS) rats, which are a well-established model for RP, received subretinal injections of hNPC and/or hNPCGDNF in one eye at different time points (21-23 days and 60 days) to assess their effect on early and late stages of retinal degeneration. The remaining eye was used as a control. At 90 days post-treatment, vision was measured and then all rats were sacrificed, and retinas were harvested and processed. Results show that subretinal injection of human neural progenitors expressing GDNF enables better visual and cellular preservation than just hNPC at both early and late stages of disease. Treatment with hNPCGDNF yielded multiple benefits, including activation of specific cell-survival pathways, reduction of oxidative stress, and promotion of cell regulation processes such as phagocytosis which improves cell health.

What this means for Usher syndrome: Previous preclinical studies demonstrated the potential of hNPC in treating RP, which resulted in an ongoing Phase 1/2a clinical trial. This new study revealed the addition of GDNF to hNPC outperformed hNPC alone for the treatment of early and late-stage RP and may become a potential therapeutic option one day.

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