RNA therapeutics
Boffa and Koschinsky review the biochemistry behind Lp(a)'s disease-causing potential as phase 3 outcome trials advance (Biochem J 2024)
Original title: Lipoprotein(a) and cardiovascular disease
This review by two leading Lp(a) biochemists examines the molecular basis of Lp(a) as a prevalent, independent, and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. It describes the salient biochemical features of the Lp(a) particle, an LDL-like lipoprotein covalently bound to the glycoprotein apolipoprotein(a), and how these features underlie its disease-causing potential, alongside the factors that determine plasma Lp(a) concentration and the mechanisms of action of emerging Lp(a)-lowering drugs, several of which are now in large phase 3 cardiovascular outcomes trials. The authors emphasise that despite this clinical progress, fundamental questions remain unanswered about Lp(a) biosynthesis, catabolism, and its true pathogenic mechanisms, framing continued basic biochemical research as essential alongside the clinical drug pipeline.
Original abstract
Elevated plasma levels of lipoprotein(a) (Lp(a)) are a prevalent, independent, and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. Lp(a) consists of a lipoprotein particle resembling low density lipoprotein and the covalently-attached glycoprotein apolipoprotein(a) (apo(a)). Novel therapeutics that specifically and potently lower Lp(a) levels are currently in advanced stages of clinical development, including in large, phase 3 cardiovascular outcomes trials. However, fundamental unanswered questions remain concerning some key aspects of Lp(a) biosynthesis and catabolism as well as the true pathogenic mechanisms of the particle. In this review, we describe the salient biochemical features of Lp(a) and apo(a) and how they underlie the disease-causing potential of Lp(a), the factors that determine plasma Lp(a) concentrations, and the mechanism of action of Lp(a)-lowering drugs.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.