Development of thymosin beta4 for treatment of patients with ischemic heart disease.

Thymosin beta 4 (Tbeta4) 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. Tbeta4 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 cytoskeletal organization, necessary for cell motility, organogenesis, and other important cellular events. Recently, Tbeta4 was shown to be expressed in the developing heart and found to stimulate migration of cardiomyocytes 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 arteriogenesis (Nature 2006). These results suggest that Tbeta4 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 Tbeta4 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 pharmacokinetics of Tbeta4 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.