Retinitis pigmentosa therapy with human embryonic stem cell- and induced pluripotent stem cell-derived photoreceptor progenitors

DESCRIPTION provided by applicant Advanced Cell Technology Inc ACT is a clinical stage biotechnology company focused on the development and commercialization of regenerative medicine and cell therapy technology The companyandapos s most advanced products are in pioneering clinical trials for the treatment of a variety of eye related debilitating diseases he overall objective of this SBIR Phase I application is to extend previous studies and provide proof of concept that human pluripotent stem cell PSC derived photoreceptor progenitors PSC PhRPs are able to prevent progression of retinitis pigmentosa RP by transplantation of PhRPs derived from human embryonic stem cells hESCs and induced pluripotent stem cells iPSCs using a rat model of RP Investigations will determine whether these grafted PSC PhRPs will promote survival of host photoreceptors and differentiate into mature photoreceptors maintain retinal connections preserve vision and rationalize further development of PhRP cell based approaches for RP therapy Retinal degenerative diseases such as RP age related macular degeneration and rod con dystrophies are characterized by loss of photoreceptor cells resulting in permanent loss of vision and often blindness currently no curative therapy exists These conditions exert extensive societal burdens on quality of life productivity and health care costs and thus an urgent need exists to develop strategies for retinal survival repair and replacement to combat RP and other degenerative diseases of the retina Recent animal studies have shown that photoreceptor cell replacement is a promising therapeutic strategy for retinal degeneration although robust cell integration and recovery of visual function has yet to be achieved Impediments to progress in the field include a limited supply of donor cells and questionable cell purity In order to overcome these barriers ACT has developed a unique method for robust differentiation of human PSCs into pure renewable populations of retinal photoreceptor cells successfully using multiple hESC and iPSC lines as starting material In initial studies ACT has demonstrated that these PSC PhRPs are able to further differentiate in vitro and form mature photoreceptors expressing rhodopsin and opsin and when transplanted into the vitreous of RCS rats differentiate into mature rod photoreceptors expressing rhodopsin and recoverin Additional preliminary studies in end stage retinal degenerated mice demonstrated that PSC PhRPs migrated and integrated into the outer nuclear layer and were therapeutically active in improving optokinetic responses In this proposal these promising studies will be extended to determine whether ACTandapos s human PSC PhRPs when grafted into retinas of RP rats are able to protect and rescue photoreceptors at an early stage of disease to limit progression of degeneration and whether they are also able to replace degenerated photoreceptors in late stage disease to restore visual function If successful IND enabling studies will initiate in a Phase II program toward eventual clinical trial PUBLIC HEALTH RELEVANCE Degenerative diseases of the eye such as retinitis pigmentosa RP and age related macular degeneration which lead to vision loss and often blindness are devastating conditions with currently no known cure Excitement in the field has recently been generated to suggest that replacing cells in the eye that normally degenerate in these diseases with healthy cells of the same type may offer a new therapeutic approach Advanced Cell Technology has developed a unique process to produce large quantities of pure human replacement cells and in this proposal will determine whether they are effective in treating RP in an animal model at both early and late stages of disease If so studies will continue toward advancing its cell based therapy approach into human clinical trials