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An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome

Marfan syndrome (MFS) is a heritable connective tissue disorder caused by pathogenic variants in the gene coding for the extracellular matrix protein fibrillin-1. While the disease affects multiple organ systems, the most life-threatening manifestations are aortic aneurysms leading to dissection and...

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Autores principales: Deleeuw, Violette, De Clercq, Adelbert, De Backer, Julie, Sips, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366784/
https://www.ncbi.nlm.nih.gov/pubmed/34408505
http://dx.doi.org/10.2147/JEP.S265271
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author Deleeuw, Violette
De Clercq, Adelbert
De Backer, Julie
Sips, Patrick
author_facet Deleeuw, Violette
De Clercq, Adelbert
De Backer, Julie
Sips, Patrick
author_sort Deleeuw, Violette
collection PubMed
description Marfan syndrome (MFS) is a heritable connective tissue disorder caused by pathogenic variants in the gene coding for the extracellular matrix protein fibrillin-1. While the disease affects multiple organ systems, the most life-threatening manifestations are aortic aneurysms leading to dissection and rupture. Other cardiovascular complications, including mitral valve prolapse, primary cardiomyopathy, and arrhythmia, also occur more frequently in patients with MFS. The standard medical care relies on cardiovascular imaging at regular intervals, along with pharmacological treatment with β-adrenergic receptor blockers aimed at reducing the aortic growth rate. When aortic dilatation reaches a threshold associated with increased risk of dissection, prophylactic surgical aortic replacement is performed. Although current clinical management has significantly improved the life expectancy of patients with MFS, no cure is available and fatal complications still occur, underscoring the need for new treatment options. In recent years, preclinical studies have identified a number of potentially promising therapeutic targets. Nevertheless, the translation of these results into clinical practice has remained challenging. In this review, we present an overview of the currently available knowledge regarding the underlying pathophysiological processes associated with MFS cardiovascular pathology. We then summarize the treatment options that have been developed based on this knowledge and are currently in different stages of preclinical or clinical development, provide a critical review of the limitations of current studies and highlight potential opportunities for future research.
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spelling pubmed-83667842021-08-17 An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome Deleeuw, Violette De Clercq, Adelbert De Backer, Julie Sips, Patrick J Exp Pharmacol Review Marfan syndrome (MFS) is a heritable connective tissue disorder caused by pathogenic variants in the gene coding for the extracellular matrix protein fibrillin-1. While the disease affects multiple organ systems, the most life-threatening manifestations are aortic aneurysms leading to dissection and rupture. Other cardiovascular complications, including mitral valve prolapse, primary cardiomyopathy, and arrhythmia, also occur more frequently in patients with MFS. The standard medical care relies on cardiovascular imaging at regular intervals, along with pharmacological treatment with β-adrenergic receptor blockers aimed at reducing the aortic growth rate. When aortic dilatation reaches a threshold associated with increased risk of dissection, prophylactic surgical aortic replacement is performed. Although current clinical management has significantly improved the life expectancy of patients with MFS, no cure is available and fatal complications still occur, underscoring the need for new treatment options. In recent years, preclinical studies have identified a number of potentially promising therapeutic targets. Nevertheless, the translation of these results into clinical practice has remained challenging. In this review, we present an overview of the currently available knowledge regarding the underlying pathophysiological processes associated with MFS cardiovascular pathology. We then summarize the treatment options that have been developed based on this knowledge and are currently in different stages of preclinical or clinical development, provide a critical review of the limitations of current studies and highlight potential opportunities for future research. Dove 2021-08-11 /pmc/articles/PMC8366784/ /pubmed/34408505 http://dx.doi.org/10.2147/JEP.S265271 Text en © 2021 Deleeuw et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Review
Deleeuw, Violette
De Clercq, Adelbert
De Backer, Julie
Sips, Patrick
An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome
title An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome
title_full An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome
title_fullStr An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome
title_full_unstemmed An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome
title_short An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome
title_sort overview of investigational and experimental drug treatment strategies for marfan syndrome
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366784/
https://www.ncbi.nlm.nih.gov/pubmed/34408505
http://dx.doi.org/10.2147/JEP.S265271
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