Abstract
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 inc...Continue Reading
References
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nabil G SeidahMichel Chretien
Dec 11, 2003·Microbiology and Molecular Biology Reviews : MMBR·Neema AgrawalSunil K Mukherjee
Jun 3, 2004·Journal of the American College of Cardiology·James H O'KeefeRobert Vogel
Jul 14, 2004·Circulation·Scott M GrundyUNKNOWN American Heart Association
Mar 10, 2005·The New England Journal of Medicine·John C LaRosaUNKNOWN Treating to New Targets (TNT) Investigators
Mar 24, 2006·The New England Journal of Medicine·Jonathan C CohenHelen H Hobbs
Jun 21, 2006·The American Journal of Cardiology·David D Waters
Dec 8, 2006·The New England Journal of Medicine·René Bernards
Feb 26, 2009·Cell·Richard W Carthew, Erik J Sontheimer
Oct 11, 2011·American Heart Journal·Salim S ViraniLaura A Petersen
Jun 5, 2012·Journal of Clinical Lipidology·Jerome D CohenTerry A Jacobson
Dec 15, 2012·American Heart Journal·Seth S MartinTracy Y Wang
Oct 8, 2013·Lancet·Kevin FitzgeraldAmy Simon
Sep 16, 2014·Atherosclerosis·Trond P Leren
Dec 2, 2014·Journal of the American Chemical Society·Jayaprakash K NairMuthiah Manoharan
Dec 9, 2014·American Journal of Therapeutics·Constantine E Kosmas, William H Frishman
Jun 20, 2015·Journal of the American College of Cardiology·Robert P Giugliano, Marc S Sabatine
Feb 27, 2016·European Heart Journal·Paul M RidkerUNKNOWN JUPITER Trial Study Group
Dec 14, 2016·The New England Journal of Medicine·Kevin FitzgeraldAmy Simon
Feb 6, 2017·Drug Discovery Today·Xuan ChiThomas Papoian
Mar 18, 2017·The New England Journal of Medicine·Marc S SabatineUNKNOWN FOURIER Steering Committee and Investigators
Mar 18, 2017·The New England Journal of Medicine·Kausik K RayJohn J P Kastelein
Jun 24, 2017·European Heart Journal·Christine LandlingerGergana Galabova
Nov 28, 2017·Journal of cardiology·Dhrubajyoti BandyopadhyaySomedeb Ball
Dec 7, 2017·Drugs in Context·Constantine E KosmasEliscer Guzman
Mar 23, 2018·Diseases·Giovanni CiccarelliGiovanni Cimmino
Citations
Mar 8, 2019·Expert Opinion on Emerging Drugs·Marilisa BoveClaudio Borghi
May 18, 2019·Expert Opinion on Drug Safety·Larysa StrilchukArrigo Fg Cicero
May 6, 2019·Science China. Life Sciences·Phei Er Saw, Er-Wei Song
May 24, 2020·Life·Agnieszka MickiewiczMarcin Gruchała
May 2, 2020·Expert Opinion on Therapeutic Targets·Federico CarboneAmirhossein Sahebkar
Jul 28, 2020·Expert Opinion on Biological Therapy·Amir Mohammad MalvandiAlberico Luigi Catapano
Jun 23, 2019·Current Cardiology Reports·Ricardo SteinFernando Scolari
Nov 30, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Charles A German, Michael D Shapiro
Jun 27, 2019·High Blood Pressure & Cardiovascular Prevention : the Official Journal of the Italian Society of Hypertension·Rita Del PintoClaudio Ferri
Dec 5, 2019·World Journal of Cardiology·Constantine E KosmasEliscer Guzman
Jul 1, 2020·Frontiers in Neuroscience·Emma M O'Connell, Falk W Lohoff
Nov 1, 2020·Nature Reviews. Cardiology·René Ernst NielsenSvend Eggert Jensen
Nov 6, 2020·Journal of Bone and Mineral Metabolism·Iván Nadir Camal RuggieriSara Feldman
Aug 12, 2019·Translational Research : the Journal of Laboratory and Clinical Medicine·Melissa L JagrosseBradley L Nilsson
Jan 14, 2020·Molecular Therapy. Nucleic Acids·Yuhua WengXing-Jie Liang
Nov 6, 2020·Therapeutics and Clinical Risk Management·Constantine E KosmasEliscer Guzman
May 1, 2021·Journal of Clinical Medicine·Ji Soo LeeFalk W Lohoff
Jun 28, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Alexandre J DebackerNagy Habib
Jul 1, 2019·Biomaterials·Weiyu ZhaoYizhou Dong
Jul 3, 2021·Journal of Clinical Medicine·Sylwester RogulaKrzysztof J Filipiak
Aug 2, 2021·Molecular Aspects of Medicine·Manish PandeyGeetanjali Chawla