878. Correction of Maternal Phenylketonuria Syndrome in the Pahenu2 Missense Mutant Mouse by r-AAV Mediated Gene Therapy

The current treatment for Phenylketonuria (PKU) is strict, lifelong, restriction of phenylalanine (Phe) in the diet. While the deleterious effects of PKU are alleviated by diet, patient compliance, especially in adults, can be poor. A second problem is the rise in Maternal PKU Syndrome, the greatly increased incidence of neurological damage in the offspring of PKU mothers who were unable to maintain good physiological control of Phe levels during pregnancy. We have previously reported long-term therapeutic correction of serum Phe levels in the Pah enu2 BTBR mouse model of PKU, using recombinant Type 2 Adeno Associated Virus vectors carrying the mouse phenylalanine hydroxylase gene (rAAV-mPAH). A second rAAV-mPAH vector now contains the WPRE element (rAAV-mPAH-WPRE). Portal vein injection of this vector into male Pah enu2 mice lowered serum phe to therapeutic levels (