VOLANESORSEN Antisense oligonucleotide targeting ApoC-III Treatment of familial chylomicronemia syndrome Treatment of hypertriglyceridemia Treatment of lipodystrophy

摘要

Elevated triglycerides have been recognized as an important factor of many pathological states and lowering them has become more and more a relevant factor in taking care of patients who suffer from the diseases associated with hypertriglyceridemia such as cardiovascular disease, obesity, metabolic syndrome and diabetes type 2. Hypertriglyceridemia is also associated with some rare diseases like familial chylomicronemia syndrome and familial partial lipodystrophy that currently have limited therapeutic options. It is therefore important to find a new agent capable of reducing levels of triglycerides to those recommended in the currently used guidelines. Apolipoprotein C-III (ApoC-III) was recognized as a multifunctional protein involved in the metabolism of triglycerides, and is responsible for various pleiotropic actions such as endothelial cell dysfunction and inflammation, dysfunction of pancreatic beta cells and counteraction of potential antiatherogenic effect of HDL particle components. It has been shown that levels of triglycerides can be lowered using antisense oligonucleotides directed against ApoC-III messenger RNA and this approach resulted in developing a new drug: volanesorsen. Its efficacy in lowering triglycerides has been shown in experimental models and in phase I and II studies. The aim of this article is to review the current knowledge about ApoC-III and its role in lipid metabolism and to present studies about volanesorsen as a novel potent therapeutic agent developed for patients with extreme hypertriglyceridemia.