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 made significant progress on our work related to the clinical development of apolipoproteinA-I mimetic peptides. We almost completed at the NIH Clinical Center a Phase I (First-in-man) clinical trial of the 5A mimetic peptide that we previously developed and tested in animal models for the treatment of cardiovascular disease. In a single dose-escalation study, we showed so far that the 5A was well tolerated and without any SAEs. There was a pause in testing it at the planned highest dose (20 mg/kg) because of access to the drug, which should be resolved soon. We recently started a new project related to ApoA5 mimetic peptides for lowering triglycerides and have developed several short peptides that show efficacy in an in vitro assay of lipolysis. Finally, we published in conjunction with collaborators at NIAID the first high-resolution structure of apolipoproteinB100 on LDL bound to its receptor by CryoEM. Understanding how LDL binds to its receptor should facilitate the future development of apolipoprotein mimetic ligands for apoB100 or other therapeutic strategies for lowering LDL.