Developing rAAV-mediated retinal gene therapy to improve vision for ZellwegerSpectrum Disorder - Year Two
Peroxisome Biogenesis Disorders of the Zellweger Spectrum (PBD-ZSD) are a group of inherited genetic disorders caused by mutations in any one of 13 PEX genes. Individuals with the common PEX1-G843D mutation consistently develop a retinopathy that progresses to blindness. To test whether we could slow visual loss in these patients, we performed a proof-of-concept trial for PEX1 retinal gene augmentation therapy using our mouse model homozygous for the equivalent PEX1-G844D mutation. We found that expression of functional PEX1 in the retina of this mouse model resulted in twofold improvement of retinal function over 6-7 months, and was effective at both earlier and later disease stages. In partnership with AmorChem Therapeutics, we will advance the preclinical, and eventually clinical, development of this therapy. Dr. Argyriou will lead the maturation plan over the 2-year Postdoctoral fellowship. The project includes experiments to establish the optimal design of the clinical gene delivery vector, dose, and efficacy, as well as establishing a business plan towards commercialization. These experiments will lead to safety and toxicology studies in nonhuman primates and an ultimate transition to the clinic.