Von Kräutern zu Pillen, Biologics und Nukleinsäuren: Das Lipid-Management der Zukunft [The lipid management of the future: From herbs to pills, biologics and nucleic acids]

Details

Ressource 1Download: 10112_von_kraeutern_und_pillen.pdf (12144.65 [Ko])
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_FC45B38001F5
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Von Kräutern zu Pillen, Biologics und Nukleinsäuren: Das Lipid-Management der Zukunft [The lipid management of the future: From herbs to pills, biologics and nucleic acids]
Journal
Cardiovascular Medicine
Author(s)
Lüscher Thomas F., von Eckardstein Arnold, Beer Jürg Hans, Räber Lorenz, Sudano Isabella, Nanchen David, Mueller Christian, Mach François, Landmesser Ul
ISSN
1662-629X
1423-5528
Publication state
Published
Issued date
2022
Peer-reviewed
Oui
Volume
25
Number
1
Pages
3-11
Language
german
Notes
L2017215176
2022-03-28
Abstract
Pharmacotherapy has made massive advances: what began with herbs and fungi led to synthetic pills that interfered ever more precisely with receptors and metabolic pathways. Finally, antibodies against specific proteins became part of our therapeutic armamentarium. But none of these measures get to the heart of the matter: The latest revolutionary chapter in pharmacotherapy uses organ-specific nucleotides, short RNAsequences that intervene in pathogenic metabolic pathways even before proteins are formed and sometimes exert a very targeted effect over surprisingly long periods of time. In cardiovascular medicine, this pharmacotherapy of the future is mainly used in the treatment of lipometabolic disorders. RNAinterference technology involving the modified small interfering RNAtherapeutic inclisiran against the messenger RNAof proprotein convertase subtilisin/kexin type 9 (PCSK9) couples the therapeutic RNAwith N-acetylgalactosamine in order to achieve liver-specific silencing of the protein formation of PCSK9 by binding to the asialoglycoprotein receptors on the surface of hepatocytes. Thus, a marked and consistent reduction of PCSK9 and LDLcholesterol levels in plasma can be achieved over more than 6 months. Other developments use antisense oligonucleotides (ASOs) against angiopoietin-like protein 3 (ANGPTL3) or apolipoprotein C-III(apoC-III) to specifically lower triglyceride levels, and the ISIS-APO(a) Rx ASO, massively reduces (>70%) the formation of lipoprotein (a). These new RNA-targeted therapeutics have key advantages, such as a long duration of action, which relates to patient compliance, the specificity of their action in certain cells or organs and metabolic pathways, and they allow for the first time an effective treatment of hypertriglyceridaemia and the mostly genetically determined elevated levels of lipoprotein (a). Large randomised clinical trials testing the effect of these new nucleic acids on cardiovascular events such as myocardial infarction and death are currently underway, including in Switzerland, and will further determine the efficacy and safety of these new drugs. This will certainly herald a new era in the treatment of various cardiovascular diseases.
Keywords
cardiovascular disease, controlled study, drug efficacy, drug safety, drug therapy, fungus, gene expression, gene silencing, heart infarction, herb, human, human tissue, hypertriglyceridemia, liver cell, nonhuman, pill, protein blood level, protein expression, protein synthesis, randomized controlled trial (topic), review, Switzerland, triacylglycerol level, angiopoietin related protein 3, antisense oligonucleotide, apolipoprotein A1, apolipoprotein C3, asialoglycoprotein, biological product, endogenous compound, inclisiran, lipid, lipoprotein A, n acetylgalactosamine, new drug, nucleic acid, nucleotide, proprotein convertase 9, protein
Open Access
Yes
Create date
31/03/2022 10:10
Last modification date
19/07/2022 7:14
Usage data