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Development of PCSK9 inhibitor to lower LDL-cholesterol |
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| รหัสดีโอไอ | |
| Creator | Wassana Riam-amatakun, Nopparat Nuntharatanapong |
| Title | Development of PCSK9 inhibitor to lower LDL-cholesterol |
| Publisher | Faculty of Pharmacy, Silpakorn University |
| Publication Year | 2561 |
| Journal Title | Thai Bulletin of Pharmaceutical Science (TBPS) |
| Journal Vol. | 13 |
| Journal No. | 1(January-June) |
| Page no. | 105-123 |
| Keyword | PCSK9, LDL-receptor, antihypercholesterolemia |
| URL Website | https://www.tci-thaijo.org/ |
| ISSN | 1686-9541 |
| Abstract | The proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in lipid metabolism by regulating LDL receptor degradation and the uptake of circulating LDL-cholesterol into the hepatic cells. PCSK9 has become an attractive agent for the treatment of hypercholesterolemia because individuals with loss-of-function mutations in gene encoding PCSK9 have lower LDL cholesterol levels than normal individuals. At present, drugs targeting PCSK9 have been designed to inhibit this enzyme through various mechanisms including PCSK9 synthesis, PCSK9 secretion or LDL-receptor binding by using inhibitors such as antisense oligonucleotides, small interfering RNA, mimetic peptides or monoclonal antibodies. PCSK9 monoclonal antibodies (mAb) are now the most successful PCSK9 inhibitors. Two PCSK9 mAb, evolocumab and alirocumab, have been approved for the treatment of hypercholesterolemia. Clinical trials have shown that these drugs effectively reduce LDL-cholesterol levels with good safety profiles. Consequently, PCSK9 mAb have become an alternative treatment for statin-intolerant patients or for those who use statiin at a maximum level, but cannot reduce the target level of cholesterol. The effect of PCSK9 mAb on cardiovascular morbidity and mortality is currently under investigation in major clinical trials. This review provides an overview of drug development against PCSK9 and the clinical efficacy of PCSK9 inhibitor antibodies in specific target populations. |
