title: Recovery of neurogenic amines in phenylketonuria mice after liver-targeted gene therapy.
abstract: Phenylketonuria (PKU) is a common genetic disorder arising from a deficiency of phenylalanine hydroxylase. If left untreated, the accumulation of phenylalanine leads to brain damage and neuropsychological dysfunction. One of the abnormalities found in hyperphenylalaninemic patients and a mouse model of PKU is an aminergic deficit in the brain. We previously showed correction of hyperphenylalaninemia and concomitant behavioral recovery in PKU mice after liver-targeted gene transfer with a viral vector. Here, we addressed whether such a functional recovery was substantiated by an improved amine metabolism in the brain. After gene transfer, brain dopamine, norepinephrine, and serotonin levels in the PKU mice were significantly elevated to normal or near-normal levels, along with systemic improvement of phenylalanine catabolism. The results of biochemical analyses validated the efficacy of PKU gene therapy in the central nervous system.
authors: Division of Genetic Therapeutics, Jichi Medical University, Shimotsuke, Japan.
authors: Hiroya
authors: H
authors: Yagi
authors: Sho
authors: S
authors: Sanechika
authors: Hiroshi
authors: H
authors: Ichinose
authors: Chiho
authors: C
authors: Sumi-Ichinose
authors: Hiroaki
authors: H
authors: Mizukami
authors: Masashi
authors: M
authors: Urabe
authors: Keiya
authors: K
authors: Ozawa
authors: Akihiro
authors: A
authors: Kume
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism*; D010651:Phenylalanine Hydroxylase / Q000235:genetics* / Q000378:metabolism; D010661:Phenylketonurias / Q000378:metabolism / Q000628:therapy*; D012701:Serotonin / Q000378:metabolism
chemical_list: D002395:Catecholamines; D018377:Neurotransmitter Agents; D012701:Serotonin; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase