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To evaluate AAV Gene Therapy in the feline model of ML II

Family portrait with three generations in matching MPS awareness tshirts

December 27, 2017

The combination of efficacy and safety data on intravenous AAV9 gene therapy from animal models and the preliminary data from human trials are highly encouraging. We therefore believe that intravenous delivery of AAV9 holds the strongest potential for effectively treating ML II and should be evaluated in the feline model of ML II.

Aim 1 of this grant proposal entailed generation and preliminary characterization of AAV vector encoding feline GNPTAB. During this reporting period we have created two AAV9 vector constructs, AAV9-Cbh-GNPTABopt-sPa and AAV9-Jet+I-GNPTABopt-SV40pA, the first driving a stronger level of expression of the GNPTAB protein and the second a weaker level of expression. Two cohorts of wild type mice have now be treated intravenously with 1 of the constructs, AAV9-Cbh-GNPTABopt-sPa or AAV9-Jet+I-GNPTABopt-SV40pA, and are currently being evaluated for safety and toxicity. Once safety and toxicity studies in mice are completed, large-scale vector manufacturing will begin to treat MLII cats in the next reporting period.

Dr. Allison Bradbury, University of Pennsylvania
Dr. Charles Vite, University of Pennsylvania
Dr. Steven Gray, University of North Carolina at Chapel Hill