Lipoprotein(a) messenger RNA (LPA mRNA) (LPA mRNA)

Lipoprotein(a) messenger RNA (LPA mRNA) is the genetic transcript of the LPA gene, which encodes apolipoprotein(a), a protein that distinguishes lipoprotein(a) [Lp(a)] from low-density lipoprotein (LDL) (Source: UniProt P08519). Synthesized almost exclusively in hepatocytes, this mRNA is the primary target for a new class of RNA-based therapeutics designed to treat hyperlipoproteinemia(a). Elevated Lp(a) is a genetically determined, independent risk factor for cardiovascular diseases, including myocardial infarction and calcific aortic valve stenosis, and is largely resistant to traditional lipid-lowering therapies like statins (Source: PubMed PMID: 35731875). Therapeutic strategies such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are designed to bind to the LPA mRNA in the liver, leading to its degradation and a subsequent reduction in the synthesis of apolipoprotein(a) (Source: PubMed PMID: 32004153). This approach has demonstrated the ability to reduce plasma Lp(a) levels by over 80-90% in clinical trials, offering a potential breakthrough for patients with high cardiovascular risk (Source: PubMed PMID: 36342163).

Other names

Apolipoprotein(a) mRNAapo(a) mRNALPA transcriptLipoprotein(a) gene transcript

The mechanism of action involves the targeted degradation of the LPA mRNA transcript in hepatocytes. Antisense oligonucleotides (ASOs) like Pelacarsen bind to the mRNA and recruit RNase H1 to cleave the RNA strand. Small interfering RNAs (siRNAs) like Olpasiran and Lepodisiran are loaded into the RNA-induced silencing complex (RISC), where the guide strand directs the cleavage of the complementary LPA mRNA. Both pathways prevent the translation of the apolipoprotein(a) protein, thereby reducing the assembly and plasma concentration of Lipoprotein(a) particles (Source: PubMed PMID: 32004153, 36342163).