TY - JOUR
T1 - Inhibition of ApoCIII: the next PCSK9?
AU - Bernelot Moens, Sophie J.
AU - van Capelleveen, Julian C.
AU - Stroes, Erik S. G.
PY - 2014
Y1 - 2014
N2 - Recent large Mendelian randomization studies associate loss-of-function mutations in apolipoprotein CIII (APOCIII) with low levels of triglycerides and decreased incidence of cardiovascular disease. With ample in-vitro and in-vivo evidence for a role of apoCIII in lipoprotein lipase-mediated triglyceride clearance and remnant removal, it is, thus, an attractive target for the treatment of hypertriglyceridemia and the prevention of cardiovascular disease. This review evaluates the current position of apoCIII in clinical practice and provides a glimpse into the future in terms of treatment options. Two large Mendelian randomization studies have shown three identical loss-of-function mutations in APOCIII to be linked to favorable lipid profiles and lower incidence of coronary artery disease. A second-generation antisense oligonucleotide, which selectively inhibits apoCIII, was able to decrease serum apoCIII and triglyceride levels in rodents, nonhuman primates and humans. The central role of apoCIII in hypertriglyceridemia and cardiovascular disease was further cemented by recent findings and promising intervention data that showed the possibility of using antisense therapy to lower apoCIII and triglyceride levels. Currently, planned phase 3 trials should provide answers in regards to long-term efficacy and safety of this novel therapy
AB - Recent large Mendelian randomization studies associate loss-of-function mutations in apolipoprotein CIII (APOCIII) with low levels of triglycerides and decreased incidence of cardiovascular disease. With ample in-vitro and in-vivo evidence for a role of apoCIII in lipoprotein lipase-mediated triglyceride clearance and remnant removal, it is, thus, an attractive target for the treatment of hypertriglyceridemia and the prevention of cardiovascular disease. This review evaluates the current position of apoCIII in clinical practice and provides a glimpse into the future in terms of treatment options. Two large Mendelian randomization studies have shown three identical loss-of-function mutations in APOCIII to be linked to favorable lipid profiles and lower incidence of coronary artery disease. A second-generation antisense oligonucleotide, which selectively inhibits apoCIII, was able to decrease serum apoCIII and triglyceride levels in rodents, nonhuman primates and humans. The central role of apoCIII in hypertriglyceridemia and cardiovascular disease was further cemented by recent findings and promising intervention data that showed the possibility of using antisense therapy to lower apoCIII and triglyceride levels. Currently, planned phase 3 trials should provide answers in regards to long-term efficacy and safety of this novel therapy
U2 - https://doi.org/10.1097/MOL.0000000000000130
DO - https://doi.org/10.1097/MOL.0000000000000130
M3 - Review article
C2 - 25255477
SN - 0957-9672
VL - 25
SP - 418
EP - 422
JO - Current opinion in lipidology
JF - Current opinion in lipidology
IS - 6
ER -