Developing autologous iPSC-RPE based IND for AMD patients

National Eye Institute

Investigators

Linked publications & trials

Abstract

1. Production of GLP-grade iPSC lines and RPE from AMD patients. Skin samples from three AMD patients were reprogrammed into GLP-grade iPSC lines and differentiated into RPE using a xeno-free medium. Generating lines from multiple patients demonstrated process consistency. The technology was successfully transferred to the NIH Clinical Center GMP facility for large-scale production. 2. Preclinical safety assessment of iPSC-RPE transplants. The clinical-grade iPSC-RPE generated in part 1 is being tested in immunocompromised animals to evaluate acute and chronic safety. Transplants are placed into the subretinal space, and histological analyses of the eye and systemic organs are performed at multiple time points to detect potential tissue damage, tumorigenesis, or teratoma formation. 3. Preclinical efficacy testing of iPSC-RPE transplants. We optimized a surgical protocol in pigs that closely models the human clinical procedure. The surgery uses a four-port vitrectomy, followed by saline injection to create a subretinal bleb between the RPE and photoreceptors. A small retinal incision allows placement of the iPSC-RPE scaffold into the subretinal space, after which the bleb is flattened by fluid-air exchange. The IND for this study was approved by the FDA in December 2019, and the clinical protocol received IRB approval in March 2020. Patient enrollment is currently ongoing. Extension to dual RPE–photoreceptor patch. In collaboration with Opsis Therapeutics, we are expanding this work to develop a dual RPE–photoreceptor patch. Proof-of-concept studies are underway to establish co-culture conditions and evaluate functionality in preclinical animal models.