Research ArticleDrug Development

Blocking endothelial lipase with monoclonal antibody MEDI5884 durably increases high density lipoprotein in nonhuman primates and in a phase 1 trial

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Science Translational Medicine  21 Apr 2021:
Vol. 13, Issue 590, eabb0602
DOI: 10.1126/scitranslmed.abb0602

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Limiting lipase to control cholesterol

Strategies to reduce low-density lipoprotein cholesterol (LDL-C) while promoting high-density lipoprotein cholesterol (HDL-C) are of interest for combating atherosclerosis. Le Lay et al. developed a monoclonal antibody that neutralizes endothelial lipase, an enzyme that hydrolyzes HDL. Antibody treatment in nonhuman primates increased plasma HDL-C, and pretreatment with a PCSK9-neutralizing antibody reduced LDL-C. Results from a phase 1 study showed that the endothelial lipase-neutralizing antibody was safe and elevated HDL-C. This approach may help reduce cardiovascular risk.

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