Development of Apo Mimetic Peptides for the Treatment Cardiovascular Disease

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

In the past year, we have made significant progress on our work related to apolipoprotein mimetic peptides based on apoA-I and apoC-II. We also started a new project on apoE mimetic peptides. In regard to the 5A apoA-I mimetic peptides, we completed single dose escalation Phase 1 study at the NIH Clinical Center. We are now in the data processing stage of the protocol but it appears that the drug was well tolerated without any SAEs. For our project related to apoC-II mimetic peptides, we recently completed and published a study on a third generation peptide based on the use of hydrocarbon staples to stabilize helix formation and to make them resistant to proteolysis. The new peptides are more potent in activating LPL than our previous apoC-II mimetic peptides and are about half the length with less amino acid changes and therefore less likely to be immunogenic. When tested in mice, the new peptides were as efective as our earlier generation and longer peptides in lowering plasma triglycerides and hence could be a potential new treatment for hypertriglyceridemia. We also used hydrocarbon staples to develop new apoE mimetic peptides, which show greater affinity as ligands for the LDL receptor than longer unstapled peptide mimetics of apoE. The new apoE mimetic peptides effectively lowered plasma lipids in apoE-KO mice. Provisional patents were filed for the apoC-II and apoE mimetic peptides with hydrocarbon staples and we are now preparing to file final patents for these two peptides.