Dr. Chi Sun from Washington University Awarded $90,000 Knights Templar Eye Foundation Grant for Pediatric Retinal Disease Gene Therapy Research

Dr. Chi Sun from Washington University St. Louis, located in St. Louis, Missouri was awarded a $90,000 grant for the research entitled: Adjunct biomolecular treatments to enhance gene therapy efficacy for CRX-associated pediatric retinal diseases.

The photoreceptors are the cells that convert incoming light into an electrical signal that can be recognized in the brain. Cone-rod homeobox (CRX) controls the photoreceptor development and make photoreceptors acquire the light-sensing function. Mutations (i.e. defective changes in DNA) in the CRX gene cause permanent damage to photoreceptors, leading to early-age vision loss. Unfortunately, these mutations can be inherited from a parent or acquired during a person’s lifetime. Treatment is unavailable at this moment. An important finding with mouse models indicates that human patients with CRX mutations may suffer from insufficient normal CRX protein in photoreceptors. Therefore, a therapeutic answer is to supply additional CRX to sick photoreceptors by gene therapy, i.e. CRX augmentation. However, the treatment outcome by a single-step CRX augmentation is promising but not utterly desirable. This study aims to develop a combination therapy of gene augmentation and drug supplements to achieve better treatment outcome. One strategy is to boost the effectiveness of CRX augmentation by a type of drug called HDAC inhibitors. They can promote genetic activities of CRX augmentation for more therapeutic actions. Another strategy is to provide protection to photoreceptors by a type of drug called neurotrophic factors. Neuroprotection benefits photoreceptor survival on top of gene therapy. This study endorses the theory of ‘1+1 is greater than 1’ for effective treatment strategies. Morphological, functional, and genetic analysis will be performed to thoroughly assess the treatment outcomes. The findings will be applicable to other preclinical trials of gene therapy dealing with early-age vision loss.