Thymosin alpha

Compounds in clinical development for the treatment of patients with HBV infection include the nucleoside analogs emtricitabine, clevudine, valtorcitabine, pradefovir, and alamifovir, as well as the immunologic modulator thymosin alpha-1, agents that facilitate uptake by the liver using conjugation to ligands, and RNA interference compounds. 

Investigational agents for the treatment of HCV infection are multiple and include inhibitors of the HCV RNA polymerase such as valopicitabine. Pis such as telaprevir, the ribavirin analogs merimepodib and viramidine, an anti-aminophospholipid antibody, a caspase inhibitor, and the immunomodulator thymosin alpha-1. 

The nucleoside analogs entecavir and clevudine, the nucleotide analog emtricitabine, and the immunologic modulators theradigm-HBV and thymosin alpha-1 are new agents under evaluation for the treatment of HBV infection. 

Lau, GJL.K., Nanji, A., Hon, X, Fong, D.Y.T., An, W.S., Yuen, S.T., Lin, M., Knng, H.F., Lam, SX. Thymosin-alpha 1 and famciclovir combination therapy activates T-cell response in patients with chronic hepatitis B virus infection in immune-tolerant phase. J. Viral Hepat. 2002" 9 280 287... 

Thymosins. Thymosins are hormone-like polypeptides produced by thymus epithelial cells. They regulate the maturation of T-cells moreover, they modulate interferon production and stimulate the expression of interleukin-2 and its receptor. A trial of thymosin fraction-5 in four homosexual patients with chronic hepatitis B demonstrated no effect after six months of treatment (202), while treatment of WHV-infected woodchucks with thymosin alpha-1 resulted in clearance of circulating WHV-DNA and a 50-300-fold decline in the levels of replicative intermediates in liver tissue (203). Subsequently, thymosin alpha-1 and thymosin fraction-5 were used to treat chronic hepatitis B in a human pilot study (204). Results were encouraging, and this was followed by several randomized, controlled multicenter trials of thymosin alpha-1 in the U.S. The primary action of thymosin is unknown, but it is probably related to its immune-enhancing effects. 

Thymosin alpha-1 is an immunomodulatory polypeptide belonging to the group of thymic hormones. It is produced endogenously... 

Observational studies The combination of thymosin alpha-1 + dacarbazine + interferon alpha has been studied in a multicenter randomized study in 488 patients with metastatic melanomas [203 ]. There were several durable responses in patients who were given thymosin alpha-1 the median duration of response was 1.9-23 months, which was sufficient to reject the null-hypothesis that the expected response rate in the treatment groups would be the same. There was also a trend towards improved progression-free survival in patients given thymosin alpha-1. Based on these results, it was concluded that thymosin alpha-1 could potentiate the efficacy of dacarbazine. The addition of thymosin alpha-1 to dacarbazine and interferon-alfa did not lead to any additional adverse reactions. 

Sinibaldi Vallebona, P., Palamara, A.T, Matteucci, C., Pierimarchi, P., Serafino, A., Mastino, A., Bistoni, F., Romani, L., and Rasi, G. (2007) Thymosin alpha 1 from bench to bedside. Annals of the New York Academy of Sciences, 1112,225-234 (b) Goldstein, A.L. and Goldstein, A.L. (2009) From lab to bedside emerging clinical applications of thymosin alpha 1. Expert Opinion on Biological Therapy, 9, 593-608. 

Thymosins A group of peptide hormones (alpha, beta, and gamma) originally described... 

The naturally occurring polypeptides alpha- and beta- Thymosins (Table 3) have been postulated to be involved in important cellular proliferation mechanisms [111] through which they can possibly influence the potential for malignant transformation of cells and provide indications as to their normal/malignant state. 

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