Testing and emerging RNA-targeted therapies for Lp(a), a review of the case for population risk screening (Cardiol Rev 2020)

The study of lipoprotein(a) [Lp(a)] over the years has been a source of both enlightenment and frustration for the medical community. Accumulating evidence from large sample observational studies, Mendelian randomization studies, and genome-wide association studies has strengthened the association between Lp(a) and the development of atherosclerotic cardiovascular disease. This evidence supports the testing of Lp(a) in certain high-risk populations in order for clinicians to improve the risk profile of patients. Despite a variety of medical therapies that have been proven to reduce Lp(a) levels, the connection between the medical management of serum Lp(a) and improved cardiovascular outcomes remains elusive, due to the lack of specificity that current therapies have in targeting the Lp(a) production pathway. A new frontier in Lp(a) research has emerged with antisense-oligonucleotide therapy and RNA interference therapy, both of which target Lp(a) production at the level of mRNA translation. These therapies provide a pathway for investigating the effect of medical management of serum Lp(a) on cardiovascular outcomes.