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Galactosemia: Towards Pharmacological Chaperones

Galactosemia is a rare inherited metabolic disease resulting from mutations in the four genes which encode enzymes involved in the metabolism of galactose. The current therapy, the removal of galactose from the diet, is inadequate. Consequently, many patients suffer lifelong physical and cognitive d...

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Autores principales: Banford, Samantha, McCorvie, Thomas J., Pey, Angel L., Timson, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914515/
https://www.ncbi.nlm.nih.gov/pubmed/33562227
http://dx.doi.org/10.3390/jpm11020106
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author Banford, Samantha
McCorvie, Thomas J.
Pey, Angel L.
Timson, David J.
author_facet Banford, Samantha
McCorvie, Thomas J.
Pey, Angel L.
Timson, David J.
author_sort Banford, Samantha
collection PubMed
description Galactosemia is a rare inherited metabolic disease resulting from mutations in the four genes which encode enzymes involved in the metabolism of galactose. The current therapy, the removal of galactose from the diet, is inadequate. Consequently, many patients suffer lifelong physical and cognitive disability. The phenotype varies from almost asymptomatic to life-threatening disability. The fundamental biochemical cause of the disease is a decrease in enzymatic activity due to failure of the affected protein to fold and/or function correctly. Many novel therapies have been proposed for the treatment of galactosemia. Often, these are designed to treat the symptoms and not the fundamental cause. Pharmacological chaperones (PC) (small molecules which correct the folding of misfolded proteins) represent an exciting potential therapy for galactosemia. In theory, they would restore enzyme function, thus preventing downstream pathological consequences. In practice, no PCs have been identified for potential application in galactosemia. Here, we review the biochemical basis of the disease, identify opportunities for the application of PCs and describe how these might be discovered. We will conclude by considering some of the clinical issues which will affect the future use of PCs in the treatment of galactosemia.
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spelling pubmed-79145152021-03-01 Galactosemia: Towards Pharmacological Chaperones Banford, Samantha McCorvie, Thomas J. Pey, Angel L. Timson, David J. J Pers Med Review Galactosemia is a rare inherited metabolic disease resulting from mutations in the four genes which encode enzymes involved in the metabolism of galactose. The current therapy, the removal of galactose from the diet, is inadequate. Consequently, many patients suffer lifelong physical and cognitive disability. The phenotype varies from almost asymptomatic to life-threatening disability. The fundamental biochemical cause of the disease is a decrease in enzymatic activity due to failure of the affected protein to fold and/or function correctly. Many novel therapies have been proposed for the treatment of galactosemia. Often, these are designed to treat the symptoms and not the fundamental cause. Pharmacological chaperones (PC) (small molecules which correct the folding of misfolded proteins) represent an exciting potential therapy for galactosemia. In theory, they would restore enzyme function, thus preventing downstream pathological consequences. In practice, no PCs have been identified for potential application in galactosemia. Here, we review the biochemical basis of the disease, identify opportunities for the application of PCs and describe how these might be discovered. We will conclude by considering some of the clinical issues which will affect the future use of PCs in the treatment of galactosemia. MDPI 2021-02-07 /pmc/articles/PMC7914515/ /pubmed/33562227 http://dx.doi.org/10.3390/jpm11020106 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Banford, Samantha
McCorvie, Thomas J.
Pey, Angel L.
Timson, David J.
Galactosemia: Towards Pharmacological Chaperones
title Galactosemia: Towards Pharmacological Chaperones
title_full Galactosemia: Towards Pharmacological Chaperones
title_fullStr Galactosemia: Towards Pharmacological Chaperones
title_full_unstemmed Galactosemia: Towards Pharmacological Chaperones
title_short Galactosemia: Towards Pharmacological Chaperones
title_sort galactosemia: towards pharmacological chaperones
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914515/
https://www.ncbi.nlm.nih.gov/pubmed/33562227
http://dx.doi.org/10.3390/jpm11020106
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