Therapeutic application of synthetic HDL for treatment of autoimmune diseases
Autoimmune diseases such as systemic lupus eritematosus (SLE) and rheumatoid arthritis (RA) had been associated with increased extent of atherosclerosis and risk of cardiovascular events. Both diseases are characterized by decreased levels of high density lipoprotein (HDL or “good” cholesterol) and changes in HDL composition. Presence of large pro-inflammatory HDL particles containing oxidized phospholipids was found in 45% of SLE patients and 20% of RA patients. HDL is a nanoparticle composed of Apoliporotein A-I (ApoA-I) and phospholipids that carriers a number of signaling lipid molecules such as sphingosine-1-phoshate (S1P). HDL also exhibits anti-oxidant and anti-inflammatory properties. The presence of anti-HDL and anti-ApoA-I antibodies has been associated with persistent disease activity in SLE patients. In this project we will explore if infusions of synthetic HDL nanoparticles with or without incorporated S1P could be a beneficial therapeutic intervention for the treatment of autoimmune diseases in murine models. We will also examine the potential mechanisms of the therapeutics benefits by measuring the levels of circulating antibodies, cytokines, and examining pathological changes/organ damage. Such novel HDL-based therapies could potentially provide dual benefit to SLE and RA patients by modulating immune response and reducing cardiovascular complications.
Published in Bioconjugate Chemistry
Published in Nature Materials
$300,000 grant from the Forbes Institute and MTRAC.
U.S. Patent Application
Presented at the Biomedical Engineering Society Annual Meeting, 2015, Tampa, FL
Presented at the Keystone Symposium on Cancer Vaccines, 2016, Whistler, BC, Canada
Published in ACS Nano, 2016
Lipid-based nanoparticles for vaccine applications. Book chapter in Biomedical Engineering: Frontier Research and Converging Technologies
Peer-reviewed book chapter