Speaker: Dr. Shannon Boye, Ph.D
Talk title: Optimizing viral gene delivery for the treatment of X-linked retinoschisis
Abstract: Mutations in RS1 are associated with X-linked retinoschisis (XLRS), a common cause of juvenile macular degeneration The presence of schisis cavities in the central retina of these patients has hampered submacular delivery with conventional Adeno associated viruses (AAVs), and clinical trials employing intravitreally injected AAVs showed lack of efficacy and inflammation. We have designed a novel AAV capsid, “AAV.SPR” that efficiently transduces photoreceptors and laterally spreads beyond the margins of the subretinal injection bleb, providing the means to perform peripheral subretinal injection without detaching the macula/fovea and deliver RS1 safely and effectively to the central retina. This talk will focus on 1) the proof concept data generated in RS1KO mice and NHPs to support the clinical development of ATSN-201and 2) the safety and efficacy observed in a Phase 1/2 clinical study of XLRS patients treated with three different doses of this gene therapy. Both preclinical and clinical results show that the ability of this novel capsid to laterally spread, enable safe and efficient transduction of the central retina following peripheral subretinal injection, and deliver therapeutic genes to larger areas of the retina make AAV.SPR an attractive option for the treatment of inherited retinal diseases including, but not limited to, XLRS.
