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 all the necessary pre-IND studies and started a Phase 1a clinical trial at the Clinical Center. We have completed the first dose cohort and expect to complete the study by 2023. For our project related to apoC-II mimetic peptides, we recently designed 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. 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. Two new provisional patents were filed for the apoC-II and apoE mimetic peptides with hydrocarbon staples.