Vaccines Targeting PSCK9 for the Treatment of Hyperlipidemia
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REVIEW
Vaccines Targeting PSCK9 for the Treatment of Hyperlipidemia Stefan Toth . Dominik Pella . Jan Fedacko
Received: June 5, 2020 Ó The Author(s) 2020
ABSTRACT Despite progress in both primary and secondary prevention, cardiovascular diseases (CVD) are still the largest group of ailments contributing to morbidity and mortality worldwide. Atherosclerotic changes, the primary pathological substrate for CVD, are closely related to hypercholesterolemia. Therefore, the treatment of hypercholesterolemia is a key therapeutic strategy for CVD management. Statins, as the gold standard in the treatment of hypercholesterolemia, have shown enhanced cardiac
Digital features To view digital features for this article go to https://doi.org/10.6084/m9.figshare.12600008. S. Toth SLOVACRIN, Slovak Clinical Research Infrastructure Network, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia D. Pella 1st Department of Cardiology, East Slovak Institute of Cardiovascular Diseases, Faculty of Medicine, Pavol Jozef Safarik University, Ondavska´ 8, 040 11 Kosˇice, Slovakia J. Fedacko (&) MEDIPARK, University Research Park for Preclinical and Clinical Research, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia e-mail: [email protected]; [email protected]
outcomes in many randomized clinical trials. However, often despite the maximum allowed and tolerated dosage of statins, we are not able to reach the target cholesterol levels, and thus patients persist at an increased cardiovascular risk. Recently, most of the large clinical studies in the field of preventive cardiology have focused on proprotein convertase subtilisin kexin type 9 (PCSK9) and its activity regulation. PCSK9 plays an essential role in the metabolism of LDL particles by inhibiting LDL receptor recirculation to the cell surface. Recent studies have shown that inhibition of PCSK9 by the administration of monoclonal antibodies is capable of significantly reducing LDL levels (up to an additional 60%) as well as reducing the incidence of CVD. However, this treatment procedure of administering the anti-PCSK9 antibodies, most frequently two times a month, has its limitations in terms of time, patient adherence, and nevertheless cost. Administration of active vaccination instead of passive immunization with anti-PCSK9 antibodies may be an effective way of controlling blood cholesterol levels. However, clinical data, as well as human testing, are still inadequate. This work aims to provide an overview of PCSK9 vaccines and their potential clinical benefit.
Keywords: Antibody; Antigen; Atherosclerosis; PCSK9; Vaccine
Cardiol Ther
Key Summary Points Methods of activation of immune system by vaccination to produce antibodies against self-antigens have been proven to be effective in several diseases such as cancer and hypertension. Several preclinical studies have manifested successful induction of anti-PCSK9 antibodies production by special epitope/ peptide vaccines, however clinical studies with sufficient results are still missing
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