Lipoprotein (a) and antisense oligonucleotides

Abstract

Background: Lipoprotein(a) (Lp(a)) was first described by geneticist Kare Berg in 1963, isolated as a new antigen (in human serum), associated with low-density lipoprotein cholesterol. Subsequently, it was reported that its levels are determined genetically and prompted a greater risk of developing atherosclerosis. For the last 20 years, evidence about the structure, genetics, and metabolic roles of Lp(a) has increased, as well as possible therapies to reduce its atherogenicity.

Objective: Provide information about the role of Lp(a) in atherosclerotic disease and evaluate new evidence about current therapies, mainly the role of antisense oligonucleotides.

Methodology: Literature review in the PubMed database, Google Scholar, and gray literature using the MeSH terms: “lipoprotein(a),” “atherosclerosis,” “physiopathology,” “therapeutics,” “drug therapy,” “oligonucleotides,” “antisense,” and by review of bibliographical references list (in "snowball") of the selected studies.

Results: There is a wide variety of bibliographic evidence about Lp(a), its importance in the development of arteriosclerotic disease, and multiple pharmacological options; both approved and under development, using this molecule as a therapeutic target.

Conclusions:  Comprehending Lp(a) mechanisms provides new explanations about the atherosclerotic cardiovascular disease; antisense oligonucleotides are currently in pharmacological development, expected to be a promising therapy to modify its concentration. However, it is necessary to await the outcomes of phase III in trials to confirm preliminary results.