Table 2.
New targets and their clinical advances
| New targets | Function | Clinical advances |
|---|---|---|
| APOC3 | APOC3 is mainly found in VLDL and chylomicron, and can stimulate liver to synthesize and secrete VLDL |
Volanesorsen was approved for use in patients with Familial chylomicemia syndrome in Europe in May 2019; Olezarsen is currently in phase 3 clinical trials; ARO-APOC3 is currently in phase 3 clinical trials |
| Lipoprotein (a) | Lp(a) is a special form of LDL particle containing 35-46% CE and 6-9% cholesterol |
Phase 2 trial of pelacarsen demonstrated significant Lp(a) lowering capacity; Olpasiran is currently in phase 3 clinical trials |
| LXRs | Activation of LXRs increases the rate of RCT by increasing ABCG1 and ABCA1 expression in macrophages but also up-regulates liver SREBP1c, leading to hepatic steatosis and hypertriglyceridemia | None |
| CETP | CETP promotes the transfer of cholesterol esters from HDL to LDL particles | Most CETP inhibitors have been discontinued for a variety of reasons. The latest CETP inhibitor, obicetrapib, is currently in phase 3 clinical trials |
| LOX-1 | LOX-1 is a scavenger receptor for oxLDL and affect the uptake of oxLDL by cells | None |
| SR-BI | Liver SR-BI regulates RCT by taking up HDL-C and transporting cholesterol to bile | None |
| LCAT | LCAT is an enzyme in plasma that esterifies cholesterol | MEDI6012 was abandoned in phase 2 for safety or efficacy reasons |
| MiR-33 and miR-122 | miR-33 inhibits expression of the genes involved in cholesterol efflux and HDL synthesis; miR-122 is the most abundant hepatic miRNA and its levels are positively correlated to human plasma cholesterol levels | None |
| Prekallikrein | Prekallikrein is identified as a binding protein of LDLR | None |