RNA therapeutics
Review takes stock of Lp(a)'s role in atherosclerosis and thrombosis while highlighting muvalaplin's oral-inhibitor promise (Int J Mol Sci 2024)
Original title: Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Where Do We Stand?
This review synthesises current understanding of Lp(a), a particle combining an LDL-like molecule with apolipoprotein(a), as an independent atherosclerotic cardiovascular disease (ASCVD) risk factor whose plasma level is 70% to 90% genetically determined through codominant LPA gene expression, making it largely stable across an individual's lifetime. The authors cover Lp(a)'s structure, metabolism, and the factors affecting its circulating levels, the challenges of standardised laboratory measurement, its role in ASCVD and thrombosis pathogenesis, and the therapeutic agents in development targeting it, including antisense oligonucleotides and small interfering RNAs. The review gives particular attention to muvalaplin, an oral inhibitor of Lp(a) formation, as a promising emerging option, framing lifelong stability and measurement difficulty as key reasons why effective Lp(a)-targeted drugs have been slow to reach the clinic.
Original abstract
Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein-like molecule and an apolipoprotein(a) [apo(a)] particle. Lp(a) has been suggested to be an independent risk factor of atherosclerotic cardiovascular disease (ASCVD). Lp(a) plasma levels are considered to be 70-90% genetically determined through the codominant expression of the LPA gene. Therefore, Lp(a) levels are almost stable during an individual's lifetime. This lifelong stability, together with the difficulties in measuring Lp(a) levels in a standardized manner, may account for the scarcity of available drugs targeting Lp(a). In this review, we synopsize the latest data regarding the structure, metabolism, and factors affecting circulating levels of Lp(a), as well as the laboratory determination measurement of Lp(a), its role in the pathogenesis of ASCVD and thrombosis, and the potential use of various therapeutic agents targeting Lp(a). In particular, we discuss novel agents, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) that are currently being developed and target Lp(a). The promising role of muvalaplin, an oral inhibitor of Lp(a) formation, is then further analyzed.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.