Development of Thymosin β4 for Treatment of Patients with Ischemic Heart Disease

摘要

Thymosin beta 4 (Tβ4) is a highly conserved, 43-amino acid acidic peptide (pI 4.6) that was first isolated from bovine thymus tissue over 25 years ago. It is present in most tissues and cell lines and is found in high concentrations in blood platelets, neutrophils, macrophages, and other lymphoid tissues. Tβ4 has numerous physiological functions, the most prominent of which being the regulation of actin polymerization in mammalian nucleated cells and with subsequent effects on actin cy-toskeletal organization, necessary for cell motility, organogenesis, and other important cellular events. Recently, Tβ4 was shown to be expressed in the developing heart and found to stimulate migration of cardiomy-ocytes and endothelial cells, promote survival of cardiomyocytes (Nature, 2004), and most recently to play an essential role in all key stages of cardiac vessel development: vasculogenesis, angiogenesis, and arteriogene-sis (Nature 2006). These results suggest that Tβ4 may have significant therapeutic potential in humans to protect myocardium and promote cardiomyocyte survival in the acute stages of ischemic heart disease. RegeneRx Biopharmaceuticals, Inc. is developing Tβ4 for the treatment of patients with acute myocardial infarction (AMI). Such efforts presented will include the formulation, development, and manufacture of a suitable drug product for use in the clinic, the performance of nonclinical pharmacology and toxicology studies, and the implementation of a phase 1 clinical protocol to assess the safety, tolerability, and the pharmacoki-netics of Tβ4 in healthy volunteers. A phase 2 proof of principle clinical trial in AMI patients is in the planning stage and will not be presented at this time.