Preclinical testing of iPSC derived retinal pigment epithelium to treat macular degeneration

Macular degeneration (MD) describes a variety of diseases that affect a specialized region of the retina called the macula. The disease impairs an individual?s ability to read, drive, and recognize faces. Age-related macular degeneration (AMD) is the most common form of MD, and is the leading cause of new cases of blindness in Americans over the age of 65 affecting ~2.1 million Americans. For ~90% of AMD patients and nearly all other MD patients, there is no cure or treatment to slow vision loss. MD results from a dysfunction of the retinal pigment epithelium (RPE). For this reason, RPE transplantation has been studied as a potential therapy for MD since the 1980?s with numerous studies demonstrating both feasibility and efficacy. However, the clinical advancement of RPE transplantation has been limited by the need for an abundant supply of RPE and a precise means for their delivery. Stem cells have been recognized since the early 2000?s as having the potential to generate a limitless supply of RPE for transplantation. However, the use of embryonic stem cells raises ethical and legal concerns. These concerns are abrogated by the use of induced pluripotent stem cells (iPSCs) which are produced by ?reprogramming? of adult somatic cells. But not all iPSC lines are equivalent. They vary greatly with regard to how ?differentiation friendly? they are and whether the processes to differentiate them are suitable for use in the manufacture of a therapeutic. In order for RPE transplantation to become a routine and successful treatment for MD, we need an abundant supply of RPE and the ability to precisely deliver an RPE monolayer to the subretinal space in the affected region of the macula using a biodegradable scaffold. Towards this goal, we have developed MRPE611. MRPE611 is a monolayer of allogeneic human iPSC-derived RPE grown on one surface of a biodegradable scaffold composed of a human fibrin hydrogel. The iPSC line used in the generation of MRPE611, 006-BIOTR-0001 clone1, is capable of producing large scale quantities of iPSC-derived RPE using processes compatible with current Good Manufacturing Processes. That iPSC line was originally created for research. The goal and single specific aim of this application is to generate a Master Cell Bank of iPSC line 006-BIOTR-0001 clone 1 and perform validation testing of the cells for use in the manufacture of RPE for use in humans. These tests will determine whether the iPSCs can meet regulatory standards for use in the manufacture of biologicals. Successful testing of the 006- BIOTR-0001 clone 1 iPSC line would permit us to advance to pre-clinical safety testing of MRPE611 in support of a future Investigational New Drug application to perform a phase 1 clinical trial of MRPE611 to treat MD.