Venous thromboembolism (VTE), a condition where blood clots form inappropriately in the veins, is estimated to affect 900,000 Americans a year. VTE can be diagnosed as deep venous thrombosis (DVT), where a clot forms deep in the veins, or as pulmonary embolism (PE), where the clot enters the lungs. Between 10 and 30% of people with VTE will die within a month of diagnosis, and about a third will experience long-term complications such as pain and swelling. Though VTE can be treated with anticoagulants, these therapies increase the risk of bleeding which can lead to complications in as many as 10% of patients, prompting a need for drugs that can treat VTE without causing bleeding.
A major goal of the Common Fund’s Glycoscience program is to make the study of carbohydrates and their roles in disease easier. Researchers funded by the Glycoscience program explored an alternative approach to treating VTE by taking advantage of the role of glycoproteins (proteins with carbohydrates attached to them) in causing the condition. A blood clot can form and grow when white blood cells and platelets (small pieces of cells found in blood) bind to each other. This binding occurs when a glycoprotein known as P-selectin glycoprotein ligand-1 (PSGL-1), found on white blood cells, binds to the protein P-selectin, found on platelets. Dr. Elliot Chaikof and colleagues used a molecule designed to mimic PSGL-1 (called P-G6) to see if it could reduce the size of blood clots by blocking the ability of PSGL-1 to bind to P-selectin. The researchers found from studies using human and mouse blood and studies using mice that P-G6 reduced platelet-white blood cell accumulation. In a mouse model of DVT, use of P-G6 reduced the size of clots without increasing bleeding. Though more research is needed to evaluate P-G6, this study highlights the promise of P-G6 as a potential new therapy for the treatment of DVT.
Reference
- A PSGL-1 glycomimetic reduces thrombus burden without affecting hemostasis. D.J. Wong, D.D. Park, S.S. Park, C.A. Haller, J. Chen, E. Dai, L. Liu, A.R. Mandhapati, P. Eradi, B. Dhakal, W.J. Wever, M. Hanes, L. Sun, R.D. Cummings, E.L. Chaikof. Blood. 2021 Sep 30; 138(13): 1182.
