PRPE-SF, polarized hESC-derived RPE Soluble Factors, as a Therapy for Early Stage Dry Age-related Macular Degeneration

It is estimated that in 2040, almost 288 million people worldwide will suffer from age-related macular degeneration (AMD), making it a leading cause of severe vison loss in the developed world. Over 5 million people globally and 1 million in the US have the advanced form of dry AMD, known as geographic atrophy (GA). In GA, large areas of supportive cells known as retinal pigment epithelium cells (RPE) degenerate over time. The loss or dysfunction of RPE becomes a key contributor to death of photoreceptors (light sensing cells) which leads to significant visual impairment in late stages of GA.  The exact cause of this devastating disease is complex and unknown, as multiple biological pathways have been implicated. As such, the development of treatments for GA has been challenging. 

Many researchers have focused their efforts on cell-based therapies that replace diseased RPE in GA with healthy cells. In general, stem cell-derived RPE have shown great promise. Through the support of CIRM,  one such cell therapy developed by our group is the CPCB-RPE1 implant, a subretinal implant containing polarized stem cell-derived RPE cells grown on a polymer scaffold. CPCB-RPE1 was designed with the intent to replace the diseased portion of GA and promote the survival and function of RPE cells. Cleared by FDA for a phase 1/2a clinical trial, all subjects treated with CPCB-RPE1 were legally blind at baseline. Twenty-seven percent of treated subjects showed improvement in vision (a ≥ 5 letter gain in best corrected visual acuity) an observation that is very rare in patients with such advanced disease. It was also observed through this work that diseased RPE cells beyond the borders of the implant survived, suggesting that the RPE cells of the CPCB-RPE1 release factors that exhibit neuroprotective properties. Subsequently, this extensive research led to the development of a novel therapeutic, polarized retinal pigmented epithelium-soluble factor (PRPE-SF). PRPE-SF is thus a byproduct of the CPCB-RPE1 implant, as it is produced from the RPE culture media that is collected at the time of production of the implant. PRPE-SF is composed of several trophic soluble factors that are secreted by RPE cells, which promote cell growth as well as exhibit many properties such as neuroprotective and anti-inflammatory effects.

PRPE-SF is intended for delivery via an intraocular injection which is a minimally invasive treatment that can be used earlier in the progression of GA. Through our translational research efforts supported by CIRM, we have demonstrated prolonged photoreceptor survival through repeated intraocular injections of PRPE-SF in preclinical studies. Hence, PRPE-SF is being developed as a potential therapy to mitigate vision loss in patients by slowing RPE degeneration and halting or significantly delaying the advancement of dry AMD. CIRM funding has allowed us to develop the manufacturing process of PRPE-SF, implement critical studies, and facilitate communication with the FDA to advance our research initiatives. Our ongoing translational work will support an investigational new biological drug application to the FDA in order to obtain approval for a first-in-human clinical trial in the treatment of GA.