Recovery of neurogenic amines in phenylketonuria mice after liver-targeted gene therapy

Hiroya Yagi, Sho Sanechika, Hiroshi Ichinose, Chiho Ichinose, Hiroaki Mizukami, Masashi Urabe, Keiya Ozawa, Akihiro Kume

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)30-34
Number of pages5
JournalNeuroReport
Volume23
Issue number1
DOIs
Publication statusPublished - 04-01-2012

Fingerprint

Phenylketonurias
Genetic Therapy
Amines
Liver
Brain
Phenylalanine
Inborn Genetic Diseases
Genes
Dopamine
Serotonin
Norepinephrine
Central Nervous System

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Yagi, Hiroya ; Sanechika, Sho ; Ichinose, Hiroshi ; Ichinose, Chiho ; Mizukami, Hiroaki ; Urabe, Masashi ; Ozawa, Keiya ; Kume, Akihiro. / Recovery of neurogenic amines in phenylketonuria mice after liver-targeted gene therapy. In: NeuroReport. 2012 ; Vol. 23, No. 1. pp. 30-34.
@article{f8524830a0474f67b81635b8727ba33b,
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.",
author = "Hiroya Yagi and Sho Sanechika and Hiroshi Ichinose and Chiho Ichinose and Hiroaki Mizukami and Masashi Urabe and Keiya Ozawa and Akihiro Kume",
year = "2012",
month = "1",
day = "4",
doi = "10.1097/WNR.0b013e32834e3a87",
language = "English",
volume = "23",
pages = "30--34",
journal = "NeuroReport",
issn = "0959-4965",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

Yagi, H, Sanechika, S, Ichinose, H, Ichinose, C, Mizukami, H, Urabe, M, Ozawa, K & Kume, A 2012, 'Recovery of neurogenic amines in phenylketonuria mice after liver-targeted gene therapy', NeuroReport, vol. 23, no. 1, pp. 30-34. https://doi.org/10.1097/WNR.0b013e32834e3a87

Recovery of neurogenic amines in phenylketonuria mice after liver-targeted gene therapy. / Yagi, Hiroya; Sanechika, Sho; Ichinose, Hiroshi; Ichinose, Chiho; Mizukami, Hiroaki; Urabe, Masashi; Ozawa, Keiya; Kume, Akihiro.

In: NeuroReport, Vol. 23, No. 1, 04.01.2012, p. 30-34.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Recovery of neurogenic amines in phenylketonuria mice after liver-targeted gene therapy

AU - Yagi, Hiroya

AU - Sanechika, Sho

AU - Ichinose, Hiroshi

AU - Ichinose, Chiho

AU - Mizukami, Hiroaki

AU - Urabe, Masashi

AU - Ozawa, Keiya

AU - Kume, Akihiro

PY - 2012/1/4

Y1 - 2012/1/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=82555168184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82555168184&partnerID=8YFLogxK

U2 - 10.1097/WNR.0b013e32834e3a87

DO - 10.1097/WNR.0b013e32834e3a87

M3 - Article

C2 - 22107842

AN - SCOPUS:82555168184

VL - 23

SP - 30

EP - 34

JO - NeuroReport

JF - NeuroReport

SN - 0959-4965

IS - 1

ER -