Inclisiran: a new promising agent in the management of hypercholesterolemia
Open accessAbstract
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.
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Inclisiran significantly decreases production of PCSK9 in liver and reduces LDL-C level, enabling management of autosomal dominant hypercholesterolemia (ADH).
“Inclisiran was reported to be able to significantly decrease the production of PCSK9 in liver and thus reduce the LDL-C level, which enables it to be used for the management of autosomal dominant hypercholesterolemia (ADH).[85, 86]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [85]
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- Authors
- Kosmas, C. E., Muñoz Estrella, A., Sourlas, A., Silverio, D., Hilario, E., Montan, P. D., & Guzman, E.
- Affiliations
- Mount Sinai Hospital (US)
- Department of Medicine, Mount Sinai St. Luke’s-West Hospital, New York, NY 10025, USA
- University of Crete (GR)
- Cardiology Clinic, Cardiology Unlimited, PC, New York, NY 10033, USA
- Montefiore Medical Center (US)
- Corresponding author
- Kosmas, Constantine E.
- Venue
- Diseases
- Publisher
- MDPI AG
- Published
- 2018-07-13
- Volume
- 6
- Issue
- 3
- Pages
- 63
- ISSN
- 2079-9721 (ISSN-L)
- PMC
- PMC6163360
- OpenAlex
- W2883175571
- Cited by
- 99
- References
- 26
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 19 · 2022: 21 · 2021: 8 · 2020: 13 · 2019: 14 · 2018: 1
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Diseases (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- inclisiran, PCSK9, hypercholesterolemia, LDL cholesterol lowering, siRNA, PCSK9 inhibition, evolocumab, alirocumab, monoclonal antibodies, statin therapy, cardiovascular risk reduction
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