RNA-based therapy in the management of lipid disorders: a review

Abstract

Abstract This review focuses on antisense oligonucleotides and small interfering ribonucleic acid therapies approved or under development for the management of lipid disorders. Recent advances in RNA-based therapeutics allow tissue-specific targeting improving safety. Multiple potential target proteins have been identified and RNA-based therapeutics have the potential to significantly improve outcomes for patients with or at risk for atherosclerotic cardiovascular disease. The advantages of RNA-based lipid modifying therapies include the ability to reduce the concentration of almost any target protein highly selectively, allowing for more precise control of metabolic pathways than can often be achieved with small molecule-based drugs. RNA-based lipid modifying therapies also make it possible to reduce the expression of target proteins for which there are no small molecule inhibitors. RNA-based therapies can also reduce pill burden as their administration schedule typically varies from weekly to twice yearly injections. The safety profile of most current RNA-based lipid therapies is acceptable but adverse events associated with various therapies targeting lipid pathways have included injection site reactions, inflammatory reactions, hepatic steatosis and thrombocytopenia. While the body of evidence for these therapies is expanding, clinical experience with these therapies is currently limited in duration and the results of long-term studies are eagerly awaited.

Keywords

• RNA-based therapies
• Lipid disorders
• Small interfering RNA
• Antisense oligonucleotides
• Lipid-lowering
• LDL-C