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Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I

Congenital deficiency of the lysosomal sialidase neuraminidase 1 (NEU1) causes the lysosomal storage disease, sialidosis, characterized by impaired processing/degradation of sialo-glycoproteins and sialo-oligosaccharides, and accumulation of sialylated metabolites in tissues and body fluids. Sialido...

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Autores principales: Mosca, Rosario, van de Vlekkert, Diantha, Campos, Yvan, Fremuth, Leigh E., Cadaoas, Jaclyn, Koppaka, Vish, Kakkis, Emil, Tifft, Cynthia, Toro, Camilo, Allievi, Simona, Gellera, Cinzia, Canafoglia, Laura, Visser, Gepke, Annunziata, Ida, d’Azzo, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141319/
https://www.ncbi.nlm.nih.gov/pubmed/32143456
http://dx.doi.org/10.3390/jcm9030695
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author Mosca, Rosario
van de Vlekkert, Diantha
Campos, Yvan
Fremuth, Leigh E.
Cadaoas, Jaclyn
Koppaka, Vish
Kakkis, Emil
Tifft, Cynthia
Toro, Camilo
Allievi, Simona
Gellera, Cinzia
Canafoglia, Laura
Visser, Gepke
Annunziata, Ida
d’Azzo, Alessandra
author_facet Mosca, Rosario
van de Vlekkert, Diantha
Campos, Yvan
Fremuth, Leigh E.
Cadaoas, Jaclyn
Koppaka, Vish
Kakkis, Emil
Tifft, Cynthia
Toro, Camilo
Allievi, Simona
Gellera, Cinzia
Canafoglia, Laura
Visser, Gepke
Annunziata, Ida
d’Azzo, Alessandra
author_sort Mosca, Rosario
collection PubMed
description Congenital deficiency of the lysosomal sialidase neuraminidase 1 (NEU1) causes the lysosomal storage disease, sialidosis, characterized by impaired processing/degradation of sialo-glycoproteins and sialo-oligosaccharides, and accumulation of sialylated metabolites in tissues and body fluids. Sialidosis is considered an ultra-rare clinical condition and falls into the category of the so-called orphan diseases, for which no therapy is currently available. In this study we aimed to identify potential therapeutic modalities, targeting primarily patients affected by type I sialidosis, the attenuated form of the disease. We tested the beneficial effects of a recombinant protective protein/cathepsin A (PPCA), the natural chaperone of NEU1, as well as pharmacological and dietary compounds on the residual activity of mutant NEU1 in a cohort of patients’ primary fibroblasts. We observed a small, but consistent increase in NEU1 activity, following administration of all therapeutic agents in most of the fibroblasts tested. Interestingly, dietary supplementation of betaine, a natural amino acid derivative, in mouse models with residual NEU1 activity mimicking type I sialidosis, increased the levels of mutant NEU1 and resolved the oligosacchariduria. Overall these findings suggest that carefully balanced, unconventional dietary compounds in combination with conventional therapeutic approaches may prove to be beneficial for the treatment of sialidosis type I.
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spelling pubmed-71413192020-04-10 Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I Mosca, Rosario van de Vlekkert, Diantha Campos, Yvan Fremuth, Leigh E. Cadaoas, Jaclyn Koppaka, Vish Kakkis, Emil Tifft, Cynthia Toro, Camilo Allievi, Simona Gellera, Cinzia Canafoglia, Laura Visser, Gepke Annunziata, Ida d’Azzo, Alessandra J Clin Med Article Congenital deficiency of the lysosomal sialidase neuraminidase 1 (NEU1) causes the lysosomal storage disease, sialidosis, characterized by impaired processing/degradation of sialo-glycoproteins and sialo-oligosaccharides, and accumulation of sialylated metabolites in tissues and body fluids. Sialidosis is considered an ultra-rare clinical condition and falls into the category of the so-called orphan diseases, for which no therapy is currently available. In this study we aimed to identify potential therapeutic modalities, targeting primarily patients affected by type I sialidosis, the attenuated form of the disease. We tested the beneficial effects of a recombinant protective protein/cathepsin A (PPCA), the natural chaperone of NEU1, as well as pharmacological and dietary compounds on the residual activity of mutant NEU1 in a cohort of patients’ primary fibroblasts. We observed a small, but consistent increase in NEU1 activity, following administration of all therapeutic agents in most of the fibroblasts tested. Interestingly, dietary supplementation of betaine, a natural amino acid derivative, in mouse models with residual NEU1 activity mimicking type I sialidosis, increased the levels of mutant NEU1 and resolved the oligosacchariduria. Overall these findings suggest that carefully balanced, unconventional dietary compounds in combination with conventional therapeutic approaches may prove to be beneficial for the treatment of sialidosis type I. MDPI 2020-03-04 /pmc/articles/PMC7141319/ /pubmed/32143456 http://dx.doi.org/10.3390/jcm9030695 Text en © 2020 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 Article
Mosca, Rosario
van de Vlekkert, Diantha
Campos, Yvan
Fremuth, Leigh E.
Cadaoas, Jaclyn
Koppaka, Vish
Kakkis, Emil
Tifft, Cynthia
Toro, Camilo
Allievi, Simona
Gellera, Cinzia
Canafoglia, Laura
Visser, Gepke
Annunziata, Ida
d’Azzo, Alessandra
Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I
title Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I
title_full Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I
title_fullStr Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I
title_full_unstemmed Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I
title_short Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I
title_sort conventional and unconventional therapeutic strategies for sialidosis type i
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141319/
https://www.ncbi.nlm.nih.gov/pubmed/32143456
http://dx.doi.org/10.3390/jcm9030695
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