Novel Therapy & Mechanism of Action

While studying why women are relatively protected against coronary artery disease until after menopause we discovered Heat Shock Protein 27 (HSP27) to be an estrogen receptor-beta associated protein.

•Extracellular HSP27 levels are inversely related to atherosclerosis (humans & mice). Lower HSP27 in patients with CAD predicts an increase risk of heart attack, stroke or death over 5 years.

•HSP27 communicates with the liver cell membrane to reduce levels of cholesterol & inflammation

•Anti-HSP27 antibodies are increased in health vs. cardiovascular disease

• HSP27 antibodies combine with HSP27 to form the HSP27 immune complex which enhances cell signaling by binding TLR4 to modulate NF-kB pathway that: 
a) upregulates expression of the LDL receptor
(= first in class “LDL-R augmenter“)
b) reduces inflammation (decrease IL-1B, IL-6; increase IL-10)

•Vaccination to increase anti-HSP27 antibodies reduces cholesterol & inflammation thereby reducing the development of atherosclerosis

Experimental Evidence that HSP27 Immunotherapy:


a) Reduces Atherosclerosis and Inflammation Levels

M=male, F=Female; rC1=recombinant control protein, rHSP25=recombinant murine form of HSP27

b) Reduces Cholesterol by ~60%

M=male, F=Female; rC1=recombinant control protein, rHSP25=recombinant murine form of HSP27

c) Upregulates Expression of the LDL-Receptor (LDL-R)

M=male, F=Female; rC1=recombinant control protein, rHSP25=recombinant murine form of HSP27

d) Involves a Novel Mechanism of Action (NF-kB Pathway)