Stem cells capable of becoming other retinal cell types, such as photoreceptors, are on the cusp of clinical trials. Although demonstration of clinical efficacy is still well behind the gene therapy field, multiple programs investigating regenerative strategies in RPE disease are beginning to enroll subjects, and initial results suggest possible signs of efficacy. It is now possible to deliver safely stem cell–derived, terminally differentiated, biologically and genetically defined retinal pigment epithelium (RPE) to the diseased human eye. Similar to gene therapy, progress in regenerative or stem cell–based transplantation strategies has been substantial. In the programs that are the furthest along-pivotal regulatory safety and efficacy trials studying individuals with retinal degeneration resulting from RPE65 mutations-initial results reveal a robust safety profile and clinically significant improvements in visual function, thereby making this program a frontrunner for the first approved gene therapy product in the United States. Additional gene-based strategies under development include approaches to autosomal dominant disease (“gain of function”), attempts to deliver genes encoding therapeutic proteins with proven mechanisms of action interfering with specific disease pathways, and approaches that could be used to render retinal cells other than atrophied photoreceptors light sensitive. Preliminary results testing gene augmentation strategies in human recessive diseases suggest promising safety and efficacy profiles, including improved visual function outcomes over extended periods. It is now possible to deliver cloned genes safely and stably to specific retinal cell types in humans. Over the past 2 decades, major advances in our understanding of the pathobiologic basis of retinal diseases, coupled with growth of gene transfer and cell transplantation biotechnologies, have created optimism that previously blinding retinal conditions may be treatable. Gene and cell therapies have the potential to prevent, halt, or reverse diseases of the retina in patients with currently incurable blinding conditions.

Steven d schwartz md avalanche