Old and New Lines of Therapy Targeting Lipoprotein(a).
Level 5 - mechanism / opinion, no new human data
Narrative review of preclinical mechanisms and ongoing clinical trials with no new data or systematic quantitative synthesis.
PubMed 42234287 · doi:10.1007/s11883-026-01419-x
What was done
The authors conducted a narrative review summarizing the evolving therapeutic landscape for elevated lipoprotein(a) [Lp(a)], synthesizing findings from preclinical studies and ongoing randomized clinical trials of targeted pharmacological and gene-based interventions.
What was found
The abstract provides no quantitative effect estimates or numerical trial data. It reports that antisense oligonucleotides (pelacarsen) and small interfering RNAs (olpasiran, lepodisiran, zerlasiran) targeting LPA gene translation are undergoing randomized clinical trials with earliest readouts expected in 2026. An oral small-molecule inhibitor (muvalaplin) lowers Lp(a) by disrupting apo(a)-apoB assembly, and CRISPR/Cas9 gene-editing has shown durable suppression of LPA expression in preclinical proof-of-concept models.
Why it matters
Elevated Lp(a) is a prevalent genetic risk factor with no currently approved targeted therapies. Ongoing phase 3 trials will determine whether pharmacologically lowering Lp(a) translates into reductions in clinical cardiovascular events.
Limits
As a narrative review, this paper presents no original empirical data, quantitative pooling, or formal risk of bias assessment. Evidence regarding clinical cardiovascular event reduction remains unknown pending the completion and readout of ongoing phase 3 outcome trials.
Cited by
- supports Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein.