RANTES and Platelet Factor 4
RANTES is a soluble chemokine secreted by many different cell types. Platelets sequester and release RANTES from α-granules during acute stages of inflammation. RANTES is a potent chemoattractant for T cells, monocytes, natural killer cells, basophils, eosinophils, and is thought to play pivotal roles in the cellular infiltrates that underlie various disease processes including atherosclerosis and airways inflammation.
Platelet factor 4 (PF4) is a small cytokine released from α-granules of activated platelets during platelet aggregation where it binds with high affinity to heparin on the endothelial surface of blood vessels to promote blood coagulation. PF4 also acts as a strong chemoattractant for neutrophils and fibroblasts and plays a role in monocyte and platelet recruitment to the arterial wall during atherosclerotic plaque development and wound repair. Elimination of PF4 from platelets reduces atherosclerosis in animal models. PF4 interacts with RANTES and heterodimers of PF4-RANTES amplify monocyte recruitment and adhesion to inflamed endothelium.
Carolus Therapeutics’ scientific founders have shown that disruption of PF4-RANTES heteromers by high affinity peptide ligands can slow the development of atherosclerotic plaque development in murine models of vascular disease (Koenen, Nature Medicine, 2009). Carolus is taking advantage of these findings and developing a proprietary peptide, CT-2008, for inflammatory diseases in which RANTES-PF4 associations exacerbates disease pathology. CT-2008 ortholog, CT-2009, has already shown positive results both in cardiovascular disease and pulmonary inflammation models. A primary development indication will be selected in the third quarter of 2010.