Cargando…

Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia

The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled....

Descripción completa

Detalles Bibliográficos
Autores principales: Kosmas, Constantine E., Muñoz Estrella, Alba, Sourlas, Andreas, Silverio, Delia, Hilario, Elizabeth, Montan, Peter D., Guzman, Eliscer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163360/
https://www.ncbi.nlm.nih.gov/pubmed/30011788
http://dx.doi.org/10.3390/diseases6030063
_version_ 1783359342367473664
author Kosmas, Constantine E.
Muñoz Estrella, Alba
Sourlas, Andreas
Silverio, Delia
Hilario, Elizabeth
Montan, Peter D.
Guzman, Eliscer
author_facet Kosmas, Constantine E.
Muñoz Estrella, Alba
Sourlas, Andreas
Silverio, Delia
Hilario, Elizabeth
Montan, Peter D.
Guzman, Eliscer
author_sort Kosmas, Constantine E.
collection PubMed
description The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled. Initially, the therapeutic approaches to reduce circulating levels of PCSK9 were focused on the use of monoclonal antibodies. To that effect, evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9, given on a background of statin therapy, have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk. The small interfering RNA (siRNA) molecules have been used recently to target the hepatic production of PCSK9. siRNA interferes with the expression of specific genes with complementary nucleotide sequences by affecting the degradation of mRNA post-transcription, thus preventing translation. Inclisiran is a long-acting, synthetic siRNA directed against PCSK9 and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels. This review aims to present and discuss the current clinical and scientific evidence pertaining to inclisiran, which is a new promising agent in the management of hypercholesterolemia.
format Online
Article
Text
id pubmed-6163360
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-61633602018-10-11 Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia Kosmas, Constantine E. Muñoz Estrella, Alba Sourlas, Andreas Silverio, Delia Hilario, Elizabeth Montan, Peter D. Guzman, Eliscer Diseases Review The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled. Initially, the therapeutic approaches to reduce circulating levels of PCSK9 were focused on the use of monoclonal antibodies. To that effect, evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9, given on a background of statin therapy, have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk. The small interfering RNA (siRNA) molecules have been used recently to target the hepatic production of PCSK9. siRNA interferes with the expression of specific genes with complementary nucleotide sequences by affecting the degradation of mRNA post-transcription, thus preventing translation. Inclisiran is a long-acting, synthetic siRNA directed against PCSK9 and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels. This review aims to present and discuss the current clinical and scientific evidence pertaining to inclisiran, which is a new promising agent in the management of hypercholesterolemia. MDPI 2018-07-13 /pmc/articles/PMC6163360/ /pubmed/30011788 http://dx.doi.org/10.3390/diseases6030063 Text en © 2018 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
Kosmas, Constantine E.
Muñoz Estrella, Alba
Sourlas, Andreas
Silverio, Delia
Hilario, Elizabeth
Montan, Peter D.
Guzman, Eliscer
Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia
title Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia
title_full Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia
title_fullStr Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia
title_full_unstemmed Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia
title_short Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia
title_sort inclisiran: a new promising agent in the management of hypercholesterolemia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163360/
https://www.ncbi.nlm.nih.gov/pubmed/30011788
http://dx.doi.org/10.3390/diseases6030063
work_keys_str_mv AT kosmasconstantinee inclisirananewpromisingagentinthemanagementofhypercholesterolemia
AT munozestrellaalba inclisirananewpromisingagentinthemanagementofhypercholesterolemia
AT sourlasandreas inclisirananewpromisingagentinthemanagementofhypercholesterolemia
AT silveriodelia inclisirananewpromisingagentinthemanagementofhypercholesterolemia
AT hilarioelizabeth inclisirananewpromisingagentinthemanagementofhypercholesterolemia
AT montanpeterd inclisirananewpromisingagentinthemanagementofhypercholesterolemia
AT guzmaneliscer inclisirananewpromisingagentinthemanagementofhypercholesterolemia