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Small-Molecule Therapeutic Perspectives for the Treatment of Progeria

Hutchinson–Gilford progeria syndrome (HGPS), or progeria, is an extremely rare disorder that belongs to the class of laminopathies, diseases characterized by alterations in the genes that encode for the lamin proteins or for their associated interacting proteins. In particular, progeria is caused by...

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Autores principales: Macicior, Jon, Marcos-Ramiro, Beatriz, Ortega-Gutiérrez, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267806/
https://www.ncbi.nlm.nih.gov/pubmed/34281245
http://dx.doi.org/10.3390/ijms22137190
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author Macicior, Jon
Marcos-Ramiro, Beatriz
Ortega-Gutiérrez, Silvia
author_facet Macicior, Jon
Marcos-Ramiro, Beatriz
Ortega-Gutiérrez, Silvia
author_sort Macicior, Jon
collection PubMed
description Hutchinson–Gilford progeria syndrome (HGPS), or progeria, is an extremely rare disorder that belongs to the class of laminopathies, diseases characterized by alterations in the genes that encode for the lamin proteins or for their associated interacting proteins. In particular, progeria is caused by a point mutation in the gene that codifies for the lamin A gene. This mutation ultimately leads to the biosynthesis of a mutated version of lamin A called progerin, which accumulates abnormally in the nuclear lamina. This accumulation elicits several alterations at the nuclear, cellular, and tissue levels that are phenotypically reflected in a systemic disorder with important alterations, mainly in the cardiovascular system, bones, skin, and overall growth, which results in premature death at an average age of 14.5 years. In 2020, lonafarnib became the first (and only) FDA approved drug for treating progeria. In this context, the present review focuses on the different therapeutic strategies currently under development, with special attention to the new small molecules described in recent years, which may represent the upcoming first-in-class drugs with new mechanisms of action endowed with effectiveness not only to treat but also to cure progeria.
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spelling pubmed-82678062021-07-10 Small-Molecule Therapeutic Perspectives for the Treatment of Progeria Macicior, Jon Marcos-Ramiro, Beatriz Ortega-Gutiérrez, Silvia Int J Mol Sci Review Hutchinson–Gilford progeria syndrome (HGPS), or progeria, is an extremely rare disorder that belongs to the class of laminopathies, diseases characterized by alterations in the genes that encode for the lamin proteins or for their associated interacting proteins. In particular, progeria is caused by a point mutation in the gene that codifies for the lamin A gene. This mutation ultimately leads to the biosynthesis of a mutated version of lamin A called progerin, which accumulates abnormally in the nuclear lamina. This accumulation elicits several alterations at the nuclear, cellular, and tissue levels that are phenotypically reflected in a systemic disorder with important alterations, mainly in the cardiovascular system, bones, skin, and overall growth, which results in premature death at an average age of 14.5 years. In 2020, lonafarnib became the first (and only) FDA approved drug for treating progeria. In this context, the present review focuses on the different therapeutic strategies currently under development, with special attention to the new small molecules described in recent years, which may represent the upcoming first-in-class drugs with new mechanisms of action endowed with effectiveness not only to treat but also to cure progeria. MDPI 2021-07-03 /pmc/articles/PMC8267806/ /pubmed/34281245 http://dx.doi.org/10.3390/ijms22137190 Text en © 2021 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 Review
Macicior, Jon
Marcos-Ramiro, Beatriz
Ortega-Gutiérrez, Silvia
Small-Molecule Therapeutic Perspectives for the Treatment of Progeria
title Small-Molecule Therapeutic Perspectives for the Treatment of Progeria
title_full Small-Molecule Therapeutic Perspectives for the Treatment of Progeria
title_fullStr Small-Molecule Therapeutic Perspectives for the Treatment of Progeria
title_full_unstemmed Small-Molecule Therapeutic Perspectives for the Treatment of Progeria
title_short Small-Molecule Therapeutic Perspectives for the Treatment of Progeria
title_sort small-molecule therapeutic perspectives for the treatment of progeria
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267806/
https://www.ncbi.nlm.nih.gov/pubmed/34281245
http://dx.doi.org/10.3390/ijms22137190
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