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What is Thymosin Alpha-1?
Thymosin alpha-1 is peptide containing 28 amino acid residues that are N-terminally acetylated and proteolytically processed from prothymosin alpha. Thymosin alpha-1 was isolated by Goldstein and coworkers from thymosin fraction 5, a mixture of peptides from calf thymus in the 1970s. It is used to improve immune responses in times of need.
Ta1 is pleiotropic – improves innate immunity when needed, down regulates immunity when not needed. Ta1 is a thymic peptide that demonstrates a profound ability to restore immune system homeostasis in different physiological and pathological conditions (i.e., viral infections, cancer, immunodeficiency, vaccination support and immunosenescence) acting as multitasking protein depending on the host state of inflammation or immune dysfunction.
Thymosin alpha-1 helps the body induce effective host-derived immune effectors and balance the Th1 / Th2 arms of immunity. These effector cells improve various immunomodulatory properties that lead to augmentation of T lymphocyte function, including modulation of interleukin-2 (IL-2), stimulation of interferon-g (IFN-g) production, induction of T lymphocyte and natural killer (NK) cells and stimulation of thymopoiesis. Ta1 has also been reported to up-regulate MHC Class I expression in antigen-presenting cells. Additionally, Ta1 down-regulates the activity of terminal deoxynucleotidyl transferase (TdT) in TdT1 thymocytes, suggesting a role for Ta1 in thymocyte maturation.
Ta1 has also been found to antagonize both activation induced (anti-CD3) and glucocorticoid-induced thymocyte apoptosis. It has also been reported that Ta1 stimulates activity of Indoleamine-2,3-Dioxygenase (IDO), leading to an increase in FoxP3 IL-10 producing regulatory T cells. This increase leads to feedback inhibition of cytokine production, hence dampening immune response to prevent a pro-inflammatory cytokine storm and possibly autoimmune phenomena.
Immune senescence, considered an aging process, has been related to a gradual decline in thymus function and thymic hormone production. The lack of thymic hormones may contribute to the decline in immune function, particularly the T cell component. In the elderly, antibody response after vaccination is compromised when compared to response in young. A similar diminished antibody response has been reported in patients with end-stage renal disease (ESRD) and in hemodialysis patients. In hemodialysis patients, this has been attributed to incompetence in T cell-mediated immune responses.
Since thymosin alpha-1 can enhance T-cell-dependent specific antibody production, Ta1 can help augment specific vaccine responses both in the elderly or in younger subjects in situations in which there are suboptimal quantities of immunizing antigen available.
Thymosin alpha-1 has been used to support immunity in over 3,000 patients and in over 70 clinical studies, either as monotherapy or in conjunction with current allopathic medicines. The lack of significant side effects with thymosin alpha-1 is in sharp contrast to other major immune response modulators such as IFN and IL-2, which can lead to flu-like symptoms including malaise, fever, headache, chills and pulmonary edema (with IL-2).
What have Research Studies Shown?
• Modulates innate immunity (pleiotropic)• Improves Th1 immune responses and helps balance Th1/Th2
• Promotes T cell (Tregs) differentiation and maturation
• Decreases T-cell apoptosis
• Improves CD3+, CD4+ and CD8+
• Improves production of IL-1 beta, IFN- γ, IL-2, IL-3, IL-6, IL-10
• Improves NK cell activity and TNF-alpha
• Improves macrophages and B cells
• Up regulates MHC Class I expression in antigen expressing cell
• Tumor specific antigens; anti-tumor properties
• Inhibits viral replication
• Activates indoleamine 2, 3-dioxygenase enzyme - dampens immunity
• Improves dendritic cell tryptophan catabolism
• Antioxidant properties – improves intracellular glutathione
• Used for clinical conditions where immune support is necessary
• Conditions requiring immune response modulation
• Hepatitis B & C
• HIV/AIDS
• Cancer – non-small cell lung (NSCLC), hepatocellular, malignant melanoma
• Chemotherapy adjunct
• Chronic inflammatory conditions; autoimmunity
• Cystic fibrosis
• Lyme disease
• Blocks steroid-induced apoptosis of thymocytes
• Depressed response to vaccinations; adjunct to flu vaccine
• Geriatric immune support
• DiGeorge’s syndrome
• May reduce hematological toxicity of cytotoxic drug therapies such as Cyclophosphamide, 5-fluorouracil (5FU), Dacarbazine, or Ifosfamide.
• Proprietary thymosin alpha-1 (thymalfasin) approved in 30 countries for hepatitis B and C and cancer
• Phase II clinical trials US – Hepatitis B
• Phase III clinical trials US – Hepatitis C
• Indicated as a monotherapy or combination therapy with interferon for the treatment of chronic hepatitis B, hepatitis C and cancer.
• Also indicated for treatment of non-small cell lung cancer (NSCLC), hepatocellular carcinoma, AIDS and malignant melanoma
Thymosin Alpha-1 in Research (Expanded)
Hepatitis BThymosin alpha-1 is indicated as a monotherapy or combination therapy with interferon for the treatment of chronic hepatitis B. Pooled analysis of 3 randomized controlled trials comprising 223 patients was performed. Thymosin alpha-1 was administered twice weekly for 6 months. Follow-up assessments were performed at 12 months after completion of treatment. In multiple studies, TA1 was reported to have a delayed therapeutic response 12 months or longer after completion of therapy.
Hepatitis C
Thymosin alpha-1 is indicated as a combination therapy with interferon for the treatment of chronic hepatitis C. Pooled analysis of 2 randomized controlled trials and 1 historical controlled trial comprising thymosin alpha-1 plus interferon, or interferon treated patients, was performed. Thymosin alpha- 1 was administered at least twice weekly for 6 to 12 months and interferon was administered up to three times weekly for 6 to 12 months. Follow-up assessments were performed upon completion of treatment and at 6 months after completion of treatment.
Cancer
Thymosin alpha-1 is indicated as a adjuvant therapy for chemotherapy-induced immune depression, immune insufficiency and immune suppression in patients with non-small cell lung carcinoma (NSCLC), malignant melanoma, hepatocellular carcinoma (HCC), breast cancer , non-Hodgkin's lymphoma (CHOP program), colorectal cancer , head and neck cancer , leukemia, pancreatic carcinoma, and renal cell carcinoma . Clinical studies in over 1,000 patients with various types of cancer demonstrated that thymosin alpha-1 improved immunological parameters, increased tumor response rates, and improved survival and quality of life (see table 3 for selected studies). Thymosin alpha-1 was either administered for 6 months or given between chemotherapy cycles for the duration of treatment.
HIV/AIDS
Both preclinical and clinical studies have shown a high degree of immune restoration from the combined administration of Ta1 and IFNα. Thus, Ta1 in combination with AZT and IFNα is reported to improve outcomes for immune suppressed HIV-infected patients.
Summary
What is Thymosin Alpha-1?Thymosin Alpha-1 is a major component of Thymosin Fraction 5 found in the thymus. The thymus is responsible for regulating the immune system. Research with Thymosin Alpha-1 has shown it to optimize the performance of immune health and general wellness by preventing infections such as the common cold or the flu. It acts to augment T-cell function; T-cells are a part of the adaptive immune system which fights off infection
How does Thymosin Alpha-1 work?
T-cells come in two forms: killer and helper cells. Killer T-cells are responsible for hunting down and destroying our body’s own cells that are cancerous or infected with bacteria or viruses. TA1 is thought to modulate the immune system by augmenting T-cell function. TA1 may affect thymocytes by stimulating their differentiation or by converting them to active T-cells.
In addition, according to the literature, Ta1 also exhibits antibacterial properties, antiviral properties, and antifungal properties. It also Increases vaccine effectiveness, suppresses tumor growth, enhances function of certain immune cells, helps eradicate unhealthy cells, stops infection or cancer growth, strengthens your immune system, and improves symptoms associated with chronic fatigue.
