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Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone(®)) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection

Cryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various Cryptococcus species. The current treatment utilizes a combination of antifungal drugs, but issues such as nephrotoxicity, restricted or limited availability in certain countries, and resistance limit thei...

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Autores principales: Alves, Vinicius, Martins, Pedro Henrique, Miranda, Bruna, de Andrade, Iara Bastos, Pereira, Luiza, Maeda, Christina Takiya, de Sousa Araújo, Glauber Ribeiro, Frases, Susana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455304/
https://www.ncbi.nlm.nih.gov/pubmed/37623554
http://dx.doi.org/10.3390/jof9080783
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author Alves, Vinicius
Martins, Pedro Henrique
Miranda, Bruna
de Andrade, Iara Bastos
Pereira, Luiza
Maeda, Christina Takiya
de Sousa Araújo, Glauber Ribeiro
Frases, Susana
author_facet Alves, Vinicius
Martins, Pedro Henrique
Miranda, Bruna
de Andrade, Iara Bastos
Pereira, Luiza
Maeda, Christina Takiya
de Sousa Araújo, Glauber Ribeiro
Frases, Susana
author_sort Alves, Vinicius
collection PubMed
description Cryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various Cryptococcus species. The current treatment utilizes a combination of antifungal drugs, but issues such as nephrotoxicity, restricted or limited availability in certain countries, and resistance limit their effectiveness. Repurposing approved drugs presents a viable strategy for developing new antifungal options. This study investigates the potential of glatiramer acetate (Copaxone(®)) as a chemotherapy candidate for Cryptococcus neoformans infection. Various techniques are employed to evaluate the effects of glatiramer acetate on the fungus, including microdilution, XTT analysis, electron and light microscopy, and physicochemical measurements. The results demonstrate that glatiramer acetate exhibits antifungal properties, with an IC(50) of 0.470 mg/mL and a minimum inhibitory concentration (MIC) of 2.5 mg/mL. Furthermore, it promotes enhanced cell aggregation, facilitates biofilm formation, and increases the secretion of fungal polysaccharides. These findings indicate that glatiramer acetate not only shows an antifungal effect but also modulates the key virulence factor—the polysaccharide capsule. In summary, repurposing glatiramer acetate as a potential chemotherapy option offers new prospects for combating C. neoformans infection. It addresses the limitations associated with current antifungal therapies by providing an alternative treatment approach.
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spelling pubmed-104553042023-08-26 Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone(®)) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection Alves, Vinicius Martins, Pedro Henrique Miranda, Bruna de Andrade, Iara Bastos Pereira, Luiza Maeda, Christina Takiya de Sousa Araújo, Glauber Ribeiro Frases, Susana J Fungi (Basel) Article Cryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various Cryptococcus species. The current treatment utilizes a combination of antifungal drugs, but issues such as nephrotoxicity, restricted or limited availability in certain countries, and resistance limit their effectiveness. Repurposing approved drugs presents a viable strategy for developing new antifungal options. This study investigates the potential of glatiramer acetate (Copaxone(®)) as a chemotherapy candidate for Cryptococcus neoformans infection. Various techniques are employed to evaluate the effects of glatiramer acetate on the fungus, including microdilution, XTT analysis, electron and light microscopy, and physicochemical measurements. The results demonstrate that glatiramer acetate exhibits antifungal properties, with an IC(50) of 0.470 mg/mL and a minimum inhibitory concentration (MIC) of 2.5 mg/mL. Furthermore, it promotes enhanced cell aggregation, facilitates biofilm formation, and increases the secretion of fungal polysaccharides. These findings indicate that glatiramer acetate not only shows an antifungal effect but also modulates the key virulence factor—the polysaccharide capsule. In summary, repurposing glatiramer acetate as a potential chemotherapy option offers new prospects for combating C. neoformans infection. It addresses the limitations associated with current antifungal therapies by providing an alternative treatment approach. MDPI 2023-07-25 /pmc/articles/PMC10455304/ /pubmed/37623554 http://dx.doi.org/10.3390/jof9080783 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alves, Vinicius
Martins, Pedro Henrique
Miranda, Bruna
de Andrade, Iara Bastos
Pereira, Luiza
Maeda, Christina Takiya
de Sousa Araújo, Glauber Ribeiro
Frases, Susana
Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone(®)) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection
title Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone(®)) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection
title_full Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone(®)) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection
title_fullStr Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone(®)) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection
title_full_unstemmed Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone(®)) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection
title_short Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone(®)) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection
title_sort assessing the in vitro potential of glatiramer acetate (copaxone(®)) as a chemotherapeutic candidate for the treatment of cryptococcus neoformans infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455304/
https://www.ncbi.nlm.nih.gov/pubmed/37623554
http://dx.doi.org/10.3390/jof9080783
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