Partial rescue of neuropathology in the murine model of PKU following administration of recombinant phenylalanine ammonia lyase (pegvaliase)

Marc Goldfinger; William L. Zeile; Carley R. Corado; Charles A. O'Neill; Laurie S. Tsuruda; Philip J. Laipis; Jonathan D. Cooper

doi:10.1016/j.ymgme.2017.04.013

Partial rescue of neuropathology in the murine model of PKU following administration of recombinant phenylalanine ammonia lyase (pegvaliase)

Marc Goldfinger, William L. Zeile, Carley R. Corado, Charles A. O'Neill, Laurie S. Tsuruda, Philip J. Laipis, Jonathan D. Cooper

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Pegylated recombinant phenylalanine ammonia lyase (pegvaliase) is an enzyme substitution therapy being evaluated for the treatment of phenylketonuria (PKU). PKU is characterized by elevated plasma phenylalanine, which is thought to lead to a deficiency in monoamine neurotransmitters and ultimately, neurocognitive dysfunction. A natural history evaluation in a mouse model of PKU demonstrated a profound decrease in tyrosine hydroxylase (TH) immunoreactivity in several brain regions, beginning at 4 weeks of age. Following treatment with pegvaliase, the number of TH positive neurons was increased in several brain regions compared to placebo treated ENU2 mice.

Original language	English
Pages (from-to)	33-35
Number of pages	3
Journal	Molecular genetics and metabolism
Volume	122
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ymgme.2017.04.013
State	Published - Sep 2017

Keywords

Phenylketonuria
Recombinant phenylalanine ammonia lyase
Tyrosine hydroxylase

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10.1016/j.ymgme.2017.04.013

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title = "Partial rescue of neuropathology in the murine model of PKU following administration of recombinant phenylalanine ammonia lyase (pegvaliase)",

abstract = "Pegylated recombinant phenylalanine ammonia lyase (pegvaliase) is an enzyme substitution therapy being evaluated for the treatment of phenylketonuria (PKU). PKU is characterized by elevated plasma phenylalanine, which is thought to lead to a deficiency in monoamine neurotransmitters and ultimately, neurocognitive dysfunction. A natural history evaluation in a mouse model of PKU demonstrated a profound decrease in tyrosine hydroxylase (TH) immunoreactivity in several brain regions, beginning at 4 weeks of age. Following treatment with pegvaliase, the number of TH positive neurons was increased in several brain regions compared to placebo treated ENU2 mice.",

keywords = "Phenylketonuria, Recombinant phenylalanine ammonia lyase, Tyrosine hydroxylase",

author = "Marc Goldfinger and Zeile, {William L.} and Corado, {Carley R.} and O'Neill, {Charles A.} and Tsuruda, {Laurie S.} and Laipis, {Philip J.} and Cooper, {Jonathan D.}",

note = "Funding Information: This study was entirely funded by BioMarin Pharmaceutical Inc. Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = sep,

doi = "10.1016/j.ymgme.2017.04.013",

language = "English",

volume = "122",

pages = "33--35",

journal = "Molecular Genetics and Metabolism",

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Partial rescue of neuropathology in the murine model of PKU following administration of recombinant phenylalanine ammonia lyase (pegvaliase). / Goldfinger, Marc; Zeile, William L.; Corado, Carley R.; O'Neill, Charles A.; Tsuruda, Laurie S.; Laipis, Philip J.; Cooper, Jonathan D.

In: Molecular genetics and metabolism, Vol. 122, No. 1-2, 09.2017, p. 33-35.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Partial rescue of neuropathology in the murine model of PKU following administration of recombinant phenylalanine ammonia lyase (pegvaliase)

AU - Goldfinger, Marc

AU - Zeile, William L.

AU - Corado, Carley R.

AU - O'Neill, Charles A.

AU - Tsuruda, Laurie S.

AU - Laipis, Philip J.

AU - Cooper, Jonathan D.

PY - 2017/9

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AB - Pegylated recombinant phenylalanine ammonia lyase (pegvaliase) is an enzyme substitution therapy being evaluated for the treatment of phenylketonuria (PKU). PKU is characterized by elevated plasma phenylalanine, which is thought to lead to a deficiency in monoamine neurotransmitters and ultimately, neurocognitive dysfunction. A natural history evaluation in a mouse model of PKU demonstrated a profound decrease in tyrosine hydroxylase (TH) immunoreactivity in several brain regions, beginning at 4 weeks of age. Following treatment with pegvaliase, the number of TH positive neurons was increased in several brain regions compared to placebo treated ENU2 mice.

KW - Phenylketonuria

KW - Recombinant phenylalanine ammonia lyase

KW - Tyrosine hydroxylase

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VL - 122

SP - 33

EP - 35

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 1-2

ER -

Partial rescue of neuropathology in the murine model of PKU following administration of recombinant phenylalanine ammonia lyase (pegvaliase)

Abstract

Keywords

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