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Thymosin β4 (Tβ4) is a peptide known for its abilities to protect and facilitate regeneration in a number of tissues following injury. Its cardioprotective effects have been evaluated in different animal models and, currently, a clinical trial is being planned in patients suffering from acute myocardial infarction. This paper focuses on the effects of Tβ4 on cardiac function in animal studies utilizing different imaging modalities for outcome measurements. [ABSTRACT FROM AUTHOR]

Studies in various animal models of disease and repair with thymosin β4 (Tβ4), the major actin-sequestering molecule in mammalian cells, have provided the scientific foundation for the ongoing dermal, corneal, and cardiac wound repair multicenter clinical trials. Tβ4 has of multiple biological activities, which include down-regulation of inflammatory chemokines and cytokines, and promotion of cell migration, blood vessel formation, cell survival, and stem cell maturation. All of these activities contribute to the multiple wound healing properties that have been observed in animal studies. This paper reviews and discusses the topical and systemic uses of Tβ4 in various animal models that demonstrate its potential for clinical use. [ABSTRACT FROM AUTHOR]

Neurorestorative therapy targets multiple types of parenchymal cells in the intact tissue of injured brain tissue to increase neurogenesis, angiogenesis, oligodendrogenesis, and axonal remodeling during recovery from neurological injury. In our laboratory, we tested thymosin β4 (Tβ4) as a neurorestorative agent to treat models of neurological injury. This review discusses our results demonstrating that Tβ4 improves neurological functional outcome in a rat model of embolic stroke, a mouse model of multiple sclerosis, and a rat model of traumatic brain injury. Tβ4 is a pleiotropic peptide exhibiting many actions in several different types of tissues. One mechanism associated with improvement of neurological improvement from Tβ4 treatment is oligodendrogenesis involving the differentiation of oligodendrocyte progenitor cells to mature myelin-secreting oligodendrocytes. Moreover, our preclinical data provide a basis for movement of Tβ4 into clinical trials for treatment of these devastating neurological diseases and injuries. [ABSTRACT FROM AUTHOR]

Inherited epidermolysis bullosa (EB), having an overall incidence of only about 19 in every 1 million live births, encompasses many phenotypically and genotypically distinct diseases characterized by the presence of recurrent blisters, mechanical fragility of the skin and other epithelial structures (most notably the cornea and gastrointestinal tract), and scar formation. Each disease is the result of mutations within any of 10 specific structural proteins (keratins, laminins, collagens, integrins) within the basilar keratinocyte or the skin basement membrane zone. Two of the more severe subtypes, junctional and dystrophic EB, often involve many extracutaneous tissues. If severe, these conditions may be life threatening. Recent studies in wounds that had been artificially induced on normal skin, both in rodents and in human volunteers, have suggested that thymosin β4 may be effective in promoting epithelial migration across the wounds. A randomized double-blind clinical trial has been recently organized to determine whether this novel biologic agent may be beneficial in promoting wound healing in patients with junctional and dystrophic EB. To do so, a solitary noninfected cutaneous wound of standardized size will be treated topically on a daily basis with either one of three concentrations of thymosin β4 or a placebo control. Serial wound healing will be quantitated by computerized digital-imaging technique. At the same time, the occurrence of adverse effects will be sought, so as to confirm the safety of thymosin β4 when applied to EB skin, both in children and in adults. Although as yet unproven, topically applied thymosin β4 may prove to be an extremely important addition to the overall management of patients with this potentially devastating disease. [ABSTRACT FROM AUTHOR]

Thymosin α 1 (Tα1), initially isolated from thymus, was characterized by Allan Goldstein in 1977. Since the beginning, our studies were aimed at evaluating its immunomodulating effects when used in combination with cytokines and chemotherapy. Combination therapies have now proved to be effective in inhibiting tumoral growth and in controlling infective diseases especially in the immunocompromised host. More recent studies showed that Tα1 molecule increased major histocompatibility complex (MHC) class-1 and Toll-like receptor expression as well as cytokine production, suggesting its immunoregulatory role. Overall these results led us to start pilot clinical trials on patients with hepatitis C and cancer. [ABSTRACT FROM AUTHOR]

After the initial dramatic effects, observed in a Lewis lung carcinoma animal model, using a combination of thymosin alpha 1 (Tα1) and interferon (IFN) after cyclophosphamide, a number of other preclinical models in mice (Friend erythroleukemia and B16 melanoma) and in rats (DHD/K12 colorectal cancer liver metastasis) have confirmed the efficacy of the combination therapy with Tα1 and either IFN or IL-2 plus chemotherapy. These results provided the scientific foundation for the first clinical trials using Tα1 in combination with BRMs and/or chemotherapy. Pivotal trials in advanced non-small cell lung cancer (NSCLC) and melanoma with Tα1 and IFN-α low doses after cis-platinum or dacarbazine produced the first evidence of the high potentiality of this approach in the treatment of human cancer. The combination of Tα1 and IFN-α was also used in patients affected by chronic B and C hepatitis including IFN-nonresponders and infected by precore mutants or genotype 1b. Further studies demonstrated additional biological activities clarifying the mechanism of action of Tα1, partially explaining the synergism with IFN. It has been shown the capacity of activating infected dendritic cells through Toll-like receptor signaling, thus influencing the inflammation balance, and of increasing the expression of tumor, viral, and major histocompatibility complex (MHC) I antigens. Dose–response studies suggested the possibility of improving the efficacy of this molecule reducing the overall toxic. Based on these information two clinical trials are ongoing: a large phase II on advanced melanoma patients treated with Tα1 at different doses after dacarbazine and a phase III one, on IFN-resistant hepatitis C virus (HCV) patients treated with a triple combination (IFN, ribavirin, and Tα1). [ABSTRACT FROM AUTHOR]