Educational guide
Designer drug for lowering triglycerides
2020 Challenge Recent genetic studies have clearly established that high levels of fat molecules called triglycerides in the blood cause heart disease. Therefore, developing drugs that reduce the amount of these fats in the bloodstream is an important area of
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2020
Challenge
Recent genetic studies have clearly established that high levels of fat molecules called triglycerides in the blood cause heart disease. Therefore, developing drugs that reduce the amount of these fats in the bloodstream is an important area of research, especially treatments for those with a genetic predisposition to high cholesterol and triglyceride levels.
Advance
IRP researchers led by senior investigator Alan T. Remaley, M.D., Ph.D., discovered a way to lower triglycerides by targeting an enzyme called lipoprotein lipase that breaks them down in the bloodstream. The researchers designed a small protein called a peptide that mimics the effect of apoC-II, a molecule that boosts the triglyceride-busting activity of lipoprotein lipase, and reduces levels of apoC-III, a molecule that inhibits lipoprotein lipase. Experiments in animals showed the peptide significantly lowers blood triglycerides and lasts long enough in the bloodstream that it could be injected only once a week as a treatment for high triglycerides.
Impact
This research has led to important insights into how apoC-II and apoC-III influence lipoprotein lipase and to the discovery of a new strategy for lowering triglycerides in the bloodstream in order to treat heart disease and genetic conditions that cause low levels of apoC-II.
Publications
Wolska A, Lo L, Sviridov DO, Pourmousa M, Pryor M, Ghosh SS, Kakkar R, Davidson M, Wilson S, Pastor RW, Goldberg IJ, Basu D, Drake SK, Cougnoux A, Wu MJ, Neher SB, Freeman LA, Tang J, Amar M, Devalaraja M, Remaley AT. (2020). A dual apolipoprotein C-II mimetic-apolipoprotein C-III antagonist peptide lowers plasma triglycerides. Sci Transl Med. Jan 29; 12(528):eaaw7905. doi: 10.1126/scitranslmed.aaw7905.
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This page was last updated on Thursday, June 8, 2023