Apolipoprotein(a) (LPA) (LPA)

The LPA gene encodes apolipoprotein(a), a specialized glycoprotein that is a defining component of the lipoprotein(a) [Lp(a)] particle (Kronenberg et al., 2022). Lp(a) consists of an LDL-like particle where apolipoprotein B-100 is disulfide-linked to apolipoprotein(a), conferring unique pro-thrombotic and pro-inflammatory properties (Tsimikas, 2017). High plasma concentrations of Lp(a) are recognized as a potent, independent, and genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (Reyes-Soffer et al., 2022). Because Lp(a) levels are largely determined by variation at the LPA genomic locus and are resistant to standard therapies like statins, the LPA mRNA has emerged as a high-priority therapeutic target. Modern therapeutic strategies utilize antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to target and degrade LPA mRNA in the liver, effectively halting the production of apolipoprotein(a) (O'Donoghue et al., 2022). Clinical trials for drugs like pelacarsen and olpasiran have demonstrated the ability to reduce circulating Lp(a) levels by over 80%, offering a potential breakthrough for patients with high cardiovascular risk (Nissen et al., 2023).

Other names

Apo(a)Lipoprotein(a) geneLPA locusApolipoprotein(a) geneLP

Antisense oligonucleotides and small interfering RNAs (siRNAs) target the LPA mRNA to prevent the translation of apolipoprotein(a), while small molecules inhibit the assembly of the lipoprotein(a) particle by blocking the interaction between apolipoprotein(a) and apolipoprotein B-100.