001 Developing treatments for pediatric genetic blindness: from bedside to bench and back

Arlene V. Drack

doi:10.1016/j.jaapos.2025.104283

Introduction We have effective treatments for many childhood ocular conditions: an opaque lens is removed by surgery; high refractive errors are expertly measured and corrected optically; strabismus and amblyopia are treated with glasses, surgery, and patching leading to lifelong improvements in quality of life. One group of conditions that has not been effectively treated is blinding genetic retinal disorders. As an investigator in the clinical trial of gene replacement for RPE65-associated Leber congenital amaurosis, I witnessed remarkable improvements in patients’ functional vision that provided proof-of-concept that other genetic retinal diseases could be treated. Methods My lab, along with collaborators, has helped develop and/or phenotype a fruit fly model of retinitis pigmentosa, mouse models of X-linked retinoschisis, and Bardet Biedl syndrome types 1 and 10, and a porcine model of CLN3 Batten disease. We developed research endpoints to detect safety and efficacy, then tested gene replacement or other treatments. The path to getting these therapies to patients will be discussed. Results Each disease and model presents unique challenges and discoveries. Among the most interesting have been analyzing the ERG in a fly, discovering that a “sham” injection is actually an effective treatment, and developing a gene therapy vector that reverses cone dysfunction in a mouse model of progressive retinal degeneration. The latter is progressing to a clinical trial. Conclusion/Relevance The strength and resilience of patients and families inspires my lab to model diseases at the research bench in order to develop new treatments for the clinic. I have learned that good science must be coupled with persistence to bring new treatments to patients. I have also learned that even as we talk about the hope of future treatments, we should celebrate all that people with vision loss can do and support accommodations that allow them to thrive.

001 Developing treatments for pediatric genetic blindness: from bedside to bench and back

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