The development of gene therapies for inherited retinal diseases (IRDs) took off when young adults and children showed significant vision improvements in an early clinical trial for what would become LUXTURNAⓇ for LCA2 (RPE65 mutations). That was 2008. LUXTURNA became the first FDA-approved IRD gene therapy in 2017. Thanks to that success, dozens of gene therapy clinical trials are underway. Some target specific genes. Others are gene-agnostic, designed to preserve photoreceptors or harness non-light-sensing cells in the retina, an approach called optogenetics.
Cell-based therapies for IRDs have not advanced so quickly, with just a few clinical trials being launched. Gene therapies, which use human-engineered viruses to deliver the therapeutic gene, are not easy to develop or administer. But cell therapies, especially those for replacing lost photoreceptors, present additional challenges that have been difficult to overcome. These include determining the source and manufacturing of the cells, promoting their survival after transplantation, and enabling their integration into the host retina.
The launch of a Phase 1/2 clinical trial for OpCT-001, an emerging photoreceptor replacement therapy from BlueRock Therapeutics, is a big step forward for the IRD cell therapy field. The trial will initially enroll people with IRDs such as retinitis pigmentosa and cone-rod dystrophy. But the approach could also be relevant for forms of LCA that primarily affect photoreceptors.
OpCT-001 is comprised of photoreceptor progenitors—photoreceptors that haven’t fully matured. Researchers believe that progenitors have the best chance of integrating and surviving once they are transplanted and mature. The progenitors are developed from induced pluripotent stem cells (iPSC). To produce iPSCs, investigators take a small blood or skin sample from an adult human donor. The cells are then genetically tweaked to revert to a stem-cell-like state. As stem cells, they can be coaxed to develop into virtually any cell type in the body, including photoreceptors. Furthermore, billions of cells (many therapy doses) can be produced from the cell sample. The study will assess several dose levels of the therapy and is expected to enroll participants in sites across the U.S.
BlueRock Therapeutics is a wholly owned subsidiary of Bayer AG. The company licensed OpCT-001 from FUJIFILM and Opsis Therapeutics, a company co-founded by David Gamm, MD, PhD, a world-renowned retinal cell therapy pioneer at the University of Wisconsin-Madison. The Foundation Fighting Blindness provided significant funding over several years to Dr. Gamm and his team for the development of retinal and photoreceptor cell therapies derived from iPSC.
One should never get too excited about any emerging therapy in an early-stage clinical trial, especially for something as cutting-edge as a photoreceptor progenitor treatment. But if there is one scientist on the planet who can get photoreceptor replacement to work, it is Dr. Gamm.
Stay tuned.