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Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice

Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency in functional phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine (Phe) in patients’ blood and organs. Affected patients encounter severe developmental delay, neurological deficits, and behavioral a...

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Autores principales: Cacicedo, Maximiliano L., Weinl-Tenbruck, Christine, Frank, Daniel, Limeres, Maria Jose, Wirsching, Sebastian, Hilbert, Katja, Pasha Famian, Mansure Abdollah, Horscroft, Nigel, Hennermann, Julia B., Zepp, Fred, Chevessier-Tünnesen, Frédéric, Gehring, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585315/
https://www.ncbi.nlm.nih.gov/pubmed/36277393
http://dx.doi.org/10.3389/fbioe.2022.993298
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author Cacicedo, Maximiliano L.
Weinl-Tenbruck, Christine
Frank, Daniel
Limeres, Maria Jose
Wirsching, Sebastian
Hilbert, Katja
Pasha Famian, Mansure Abdollah
Horscroft, Nigel
Hennermann, Julia B.
Zepp, Fred
Chevessier-Tünnesen, Frédéric
Gehring, Stephan
author_facet Cacicedo, Maximiliano L.
Weinl-Tenbruck, Christine
Frank, Daniel
Limeres, Maria Jose
Wirsching, Sebastian
Hilbert, Katja
Pasha Famian, Mansure Abdollah
Horscroft, Nigel
Hennermann, Julia B.
Zepp, Fred
Chevessier-Tünnesen, Frédéric
Gehring, Stephan
author_sort Cacicedo, Maximiliano L.
collection PubMed
description Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency in functional phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine (Phe) in patients’ blood and organs. Affected patients encounter severe developmental delay, neurological deficits, and behavioral abnormalities when not treated. Early diagnosis and treatment are extremely important; newborn screening programs have been implemented in most countries to ensure early identification of patients with PKU. Despite available treatment options, several challenges remain: life-long adherence to a strict diet, approval of some medications for adults only, and lack of response to these therapies in a subpopulation of patients. Therefore, there is an urgent need for treatment alternatives. An mRNA-based approach tested in PKU mice showed a fast reduction in the accumulation of Phe in serum, liver and brain, the most significant organ affected. Repeated injections of LNP-formulated mouse PAH mRNA rescued PKU mice from the disease phenotype for a prolonged period of time. An mRNA-based approach could improve the quality of life tremendously in PKU patients of all ages by replacing standard-of-care treatments.
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spelling pubmed-95853152022-10-22 Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice Cacicedo, Maximiliano L. Weinl-Tenbruck, Christine Frank, Daniel Limeres, Maria Jose Wirsching, Sebastian Hilbert, Katja Pasha Famian, Mansure Abdollah Horscroft, Nigel Hennermann, Julia B. Zepp, Fred Chevessier-Tünnesen, Frédéric Gehring, Stephan Front Bioeng Biotechnol Bioengineering and Biotechnology Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency in functional phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine (Phe) in patients’ blood and organs. Affected patients encounter severe developmental delay, neurological deficits, and behavioral abnormalities when not treated. Early diagnosis and treatment are extremely important; newborn screening programs have been implemented in most countries to ensure early identification of patients with PKU. Despite available treatment options, several challenges remain: life-long adherence to a strict diet, approval of some medications for adults only, and lack of response to these therapies in a subpopulation of patients. Therefore, there is an urgent need for treatment alternatives. An mRNA-based approach tested in PKU mice showed a fast reduction in the accumulation of Phe in serum, liver and brain, the most significant organ affected. Repeated injections of LNP-formulated mouse PAH mRNA rescued PKU mice from the disease phenotype for a prolonged period of time. An mRNA-based approach could improve the quality of life tremendously in PKU patients of all ages by replacing standard-of-care treatments. Frontiers Media S.A. 2022-10-07 /pmc/articles/PMC9585315/ /pubmed/36277393 http://dx.doi.org/10.3389/fbioe.2022.993298 Text en Copyright © 2022 Cacicedo, Weinl-Tenbruck, Frank, Limeres, Wirsching, Hilbert, Pasha Famian, Horscroft, Hennermann, Zepp, Chevessier-Tünnesen and Gehring. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Cacicedo, Maximiliano L.
Weinl-Tenbruck, Christine
Frank, Daniel
Limeres, Maria Jose
Wirsching, Sebastian
Hilbert, Katja
Pasha Famian, Mansure Abdollah
Horscroft, Nigel
Hennermann, Julia B.
Zepp, Fred
Chevessier-Tünnesen, Frédéric
Gehring, Stephan
Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice
title Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice
title_full Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice
title_fullStr Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice
title_full_unstemmed Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice
title_short Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice
title_sort phenylalanine hydroxylase mrna rescues the phenylketonuria phenotype in mice
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585315/
https://www.ncbi.nlm.nih.gov/pubmed/36277393
http://dx.doi.org/10.3389/fbioe.2022.993298
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