Aiming Even Lower

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Science  04 May 2012:
Vol. 336, Issue 6081, pp. 521
DOI: 10.1126/science.336.6081.521-a

The use of statins to lower plasma levels of LDL (low-density lipoprotein) cholesterol can reduce the risk of cardiovascular disease by an estimated 30 to 40%. Yet some experts have argued that lowering LDL cholesterol to levels below current recommendations—by coadministering drugs that act by a complementary mechanism, for example—may confer even more health benefits than statins alone. PCSK9 (proprotein convertase subtilisin/kexin type 9) is an appealing new drug target because it keeps plasma cholesterol levels high by promoting degradation of the receptor on liver cells that removes cholesterol from the blood. Interestingly, a small percentage of humans carry mutations in PCSK9 that reduce its activity and these individuals have a lower risk of heart disease, suggesting that therapeutic inhibition of PCSK9 will be safe. Stein et al. conducted small phase-1 trials of a human PCSK9 monoclonal antibody (REGN727) given to healthy volunteers and to individuals with familial and nonfamilial hypercholesterolemia. Injection of REGN727 induced no serious adverse effects in these short-duration trials, and in all groups the antibody significantly reduced LDL cholesterol levels as compared with placebo.

N. Engl. J. Med. 366, 1108 (2012).

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