Cholesterol Lowering Biotechnological Strategies: From Monoclonal Antibodies to Antisense Therapies. A Pre-Clinical Perspective Review

被引:6
作者
Bellosta, S. [1 ]
Rossi, C. [1 ]
Alieva, A. S. [1 ,2 ]
Catapano, A. L. [1 ,3 ]
Corsini, A. [1 ,3 ]
Baragetti, A. [1 ,3 ]
机构
[1] Univ Milan, Dept Pharmacol & Biomol Sci, Via Balzaretti 9, I-20133 Milan, Italy
[2] Almazov Natl Med Res Ctr, St Petersburg, Russia
[3] IRCCS MultiMedica, Via Fantoli 16, I-20138 Milan, Italy
关键词
Angptl3; Car-T therapy; LDLR; Lp(a); mAb; PCSK9; SUBTILISIN/KEXIN TYPE 9; APOLIPOPROTEIN C-III; LDL-CHOLESTEROL; IN-VIVO; PLASMINOGEN-ACTIVATOR; HEALTHY-VOLUNTEERS; PCSK9; RNA; OLIGONUCLEOTIDE; ANGPTL3;
D O I
10.1007/s10557-021-07293-w
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In recent years, the increase in available genetic information and a better understanding of the genetic bases of dyslipidemias has led to the identification of potential new avenues for therapies. Additionally, the development of new technologies has presented the key for developing novel therapeutic strategies targeting not only proteins (e.g., the monoclonal antibodies and vaccines) but also the transcripts (from antisense oligonucleotides (ASOs) to small interfering RNAs) or the genomic sequence (gene therapies). These pharmacological advances have led to successful therapeutic improvements, particularly in the cardiovascular arena because we are now able to treat rare, genetically driven, and previously untreatable conditions (e.g, familial hypertriglyceridemia or hyperchylomicronemia). In this review, the pre-clinical pharmacological development of the major biotechnological cholesterol lowering advances were discussed, describing facts, gaps, potential future steps forward, and therapeutic opportunities.
引用
收藏
页码:585 / 598
页数:14
相关论文
共 88 条
[1]   Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance [J].
Adam, Rene C. ;
Mintah, Ivory J. ;
Alexa-Braun, Corey A. ;
Shihanian, Lisa M. ;
Lee, Joseph S. ;
Banerjee, Poulabi ;
Hamon, Sara C. ;
Kim, Hye In ;
Cohen, Jonathan C. ;
Hobbs, Helen H. ;
Van Hout, Cristopher ;
Gromada, Jesper ;
Murphy, Andrew J. ;
Yancopoulos, George D. ;
Sleeman, Mark W. ;
Gusarova, Viktoria .
JOURNAL OF LIPID RESEARCH, 2020, 61 (09) :1271-1286
[2]   N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels [J].
Alexander, Veronica J. ;
Xia, Shuting ;
Hurh, Eunju ;
Hughes, Steven G. ;
O'Dea, Louis ;
Geary, Richard S. ;
Witztum, Joseph L. ;
Tsimikas, Sotirios .
EUROPEAN HEART JOURNAL, 2019, 40 (33) :2785-2796
[3]   INHIBITION OF APOLIPOPROTEIN C-III WITH GALNAC CONJUGATED ANTISENSE DRUG POTENTLY LOWERS FASTING SERUM APOLIPOPROTEIN C-III AND TRIGLYCERIDE LEVELS IN HEALTHY VOLUNTEERS WITH ELEVATED TRIGLYCERIDES [J].
Alexander, Veronica J. ;
Digenio, Andres ;
Xia, Shuting ;
Hurh, Eunju ;
Hughes, Steve ;
Geary, Richard S. ;
Witztum, Joseph L. ;
Tsimikas, Sotirios .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2018, 71 (11) :1724-1724
[4]  
[Anonymous], 2014, AMGEN EVOLOCUMAB AMG
[5]  
[Anonymous], 2014, REGENERON ALIROCUMAB
[6]   Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials [J].
Baigent, C. ;
Blackwell, L. ;
Emberson, J. ;
Holland, L. E. ;
Reith, C. ;
Bhala, N. ;
Peto, R. ;
Barnes, E. H. ;
Keech, A. ;
Simes, J. ;
Collins, R. .
LANCET, 2010, 376 (9753) :1670-1681
[7]   Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia [J].
Banerjee, Yajnavalka ;
Pantea Stoian, Anca ;
Cicero, Arrigo Francesco Giuseppe ;
Fogacci, Federica ;
Nikolic, Dragana ;
Sachinidis, Alexandros ;
Rizvi, Ali A. ;
Janez, Andrej ;
Rizzo, Manfredi .
EXPERT OPINION ON DRUG SAFETY, 2022, 21 (01) :9-20
[8]   Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia [J].
Bhatt, Deepak L. ;
Steg, P. Gabriel ;
Miller, Michael ;
Brinton, Eliot A. ;
Jacobson, Terry A. ;
Ketchum, Steven B. ;
Doyle, Ralph T., Jr. ;
Juliano, Rebecca A. ;
Jiao, Lixia ;
Granowitz, Craig ;
Tardif, Jean-Claude ;
Ballantyne, Christie M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2019, 380 (01) :11-22
[9]   Apolipoprotein(a) attenuates endogenous fibrinolysis in the rabbit jugular vein thrombosis model in vivo [J].
Biemond, BJ ;
Friederich, PW ;
Koschinsky, ML ;
Levi, M ;
Sangrar, W ;
Xia, JZ ;
Buller, HR ;
tenCate, JW .
CIRCULATION, 1997, 96 (05) :1612-1615
[10]   Potent reduction of plasma lipoprotein (a) with an antisense oligonucleotide in human subjects does not affect ex vivo fibrinolysis[S] [J].
Boffa, Michael B. ;
Marar, Tanya T. ;
Yeang, Calvin ;
Viney, Nicholas J. ;
Xia, Shuting ;
Witztum, Joseph L. ;
Koschinsky, Marlys L. ;
Tsimikas, Sotirios .
JOURNAL OF LIPID RESEARCH, 2019, 60 (12) :2082-2089