Developing treatment option for vision loss through transplant of photoreceptor precursors

Retinal progenitor cells derived from RxCell induced pluripotent stem cells (iPSCs) can mature into retina photoreceptors after transplantation into the preclinical models, enabling restored vision. (Image courtesy of NUS Yong Loo Lin School of Medicine)

Inherited retinal diseases (IRDs) are a group of genetically and clinically homogeneous illnesses characterized by progressive retinal damage leading to vision loss. 

With the global incidence of IRDs at approximately 1 in 2000 persons, these disorders are among the leading causes of blindness worldwide.

The introduction of gene therapy has proven to be a significant medical breakthrough, though its effectiveness has been blunted by the extent of genetic heterogeneity, with more than 260 genes implicated in IRDs.

This limits the widespread application of gene therapy for all IRDs.

Moreover, gene therapy has limited efficacy in clinical cases of advanced retinal degeneration in which significant photoreceptor cell death has already occurred.

Photoreceptor cells are found in the retina and respond to light, converting it into electrical signals that activate physiological chain reactions. These signals are sent through the optic nerve to the brain for processing.

With the introduction of induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) technology, regenerative stem cell therapy has the potential to be an alternative treatment for end-stage retinal degeneration, independent of the underlying genetic defect. Retinal regenerative therapies therefore hold great promise for the treatment of IRDs.

Studies in animal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, though there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals.

A study¹ led by Su Xinyi, PhD, an assistant professor in the Department of Ophthalmology at the NUS Yong Loo Lin School of Medicine, examines the therapeutic potential of photoreceptor precursors derived from clinically compliant iPSCs.

Investigators demonstrated the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials.

According to investigators, these include performing a first-in-man clinical trial for photoreceptor precursor transplant in Singapore, in collaboration with RxCELL, a biotechnology company focused on therapeutic applications iPSCs.

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Reference

1. Su Xinyi, et al. “cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates;” Stem Cell Research & Therapy; Aug. 19, 2021.