Description
Thymosin Alpha-1 for sale
Thymosin alpha-1 peptide, also known as Thymosin alpha, or TA1, or T α 1, is a fragment of a protein molecule. In various studies, Thymosin alpha-1 benefits have been:
- Thymosin alpha-1 has been shown to boost the body’s immune system
- Thymosin alpha boosts the number of T-cells which in turn protect the body from infections, such as bacteria and viruses
- It helps regulate inflammation related to autoimmune diseases such as rheumatoid arthritis, lupus, and others
What is Thymosin Alpha-1 Peptide?
Immunodeficiency, as the name suggests, is the weakening of the human immune system and its ability to fight disorders. Immunodeficiency is classified into two categories, namely primary immune deficiency disorders and secondary immune deficiency disorders. Primary immune deficiency disorders are genetic, inherited diseases that are usually diagnosed at an early stage in life; whereas secondary immune deficiency disorders are acquired disorders caused by underlying disease or by environment (1).
As per recent statistics, there are more than 200 different forms of immune deficiency disorders affecting nearly 500,000 people in the US alone (2).
While medications are available and being researched on to treat and control these disorders, there is one peptide that is infused in patients suffering from such immunodeficiency, in order to stimulate and maintain the immune system efficiency – and this peptide is known as Thymosin alpha-1.
Introduction
Thymosin alpha-1 is a naturally occurring polypeptide found in the thymus gland in humans, which helps to restore and enhance body immune functions (3).
Thymosin alpha-1 is considered to be one of the polypeptides found in Thymosin fraction 5, which is a crude extract of the thymus gland (4).
Since its discovery, synthetic form of Thymosin alpha-1 has also been developed which is called Thymalfasin (3). Thymalfasin is composed of 28 amino acids, similar to the naturally occurring Thymosin alpha 1, and is derived from a longer polypeptide precursor composed of 113 amino acids, known as prothymosin alpha (4).
History of Peptide
Thymosin alpha-1 peptide was first isolated from the thymus gland and characterized in 1977 by Allan Goldstein (5).
The main aim of the initial studies (5) was to understand and examine the immunomodulating effects of the peptide when used in combination with chemotherapy. Studies have since shown that the peptide increases the concentrations of the major histocompatibility complex (MHC) class I and cytokine production, which leads to increased immune responses in the human system. Owing to these immunoregulatory properties, these studies indicated that the peptide could be used in patients suffering from immunodeficiency disorders.
Thymosin alpha-1 Synthesis
There are three main routes by which the synthesis of the peptide takes place (3):
1. First method is the isolation of Thymosin fraction 5 from the calf thymuses, and thereby subsequent extraction of Thymosin alpha. This extraction technique was first discovered in 1975.
2. Second method is via solid phase synthesis. This is a purely chemical method and the only method used nowadays for the peptide production and its clinical use.
3. Lastly, genetic engineering expression is the third method by which the peptide can be synthesized – recombinant Thymosin alpha 1 can be derived from either the unicellular (E.coli) or multicellular organisms (Yeast, plants).
Mode of Action
Thymosin alpha-1 stimulates its effects mainly by targeting the T-helper cells and cytotoxic T-cell populations (4).
Thymosin alpha-1 induces differentiation of the T-cells (thymocytes) and the terminal differentiation of the blood lymphocytes. It elevates the production of the natural killer cells and stimulates cytokine mediated inflammation (3,4). Furthermore, the peptide also enhances the efficiency of macrophages and functions as the modulator of the alpha thrombin activity (4).
Benefits of Thymosin alpha 1 Peptide
As mentioned, Thymosin alpha 1 has the key benefit of fighting immunodeficiency by increasing body immune functions. Due to this, the peptide has several health benefits, including (3):
- Increases immune response to fight several bacterial, viral and fungal infections
- Possess anti-cancer and anti-tumor properties – by enhancing the T-cell maturation into CD4/CD8+ T cells
- Immunomodulatory properties – by stimulating cytokine expression
- Controls inflammation and tolerance levels
- FDA approved medication to treat malignant melanoma, hepatitis, hepatocellular carcinoma
- Promising candidate to treat HIV infection
- Helps to decrease toxicity caused by chemotherapy
- Influenza vaccine co-adjuvant – upon co-administration along with the influenza vaccine in immunocompromised patients, it enhances the body immune response (10)
Thymosin alpha Clinical Studies
Various clinical studies have been carried out to examine the use of Thymosin alpha-1 peptide in several human immunodeficiency disorders, as listed below.
Primary Immunodeficiencies
In this 1990s study (6), 11 patients with different immune deficiencies were used as clinical trial subjects to examine the levels of their natural killer (NK) and lymphokine activated killer cells.
It was noted that the immunodeficient patients demonstrated the mean LAK-cell activity of approximately 65% as compared to the healthy volunteers. Administration of Thymosin alpha-1 did not significantly improve their levels. Only 3 patients showed an improved LAK-cell activity by up to 30% whereas others were not significantly impacted. Interestingly, there was one patient who showed no impact in their LAK-cell activity even after the peptide administration in vitro.
These results demonstrated that depending on the individual body profile and immunomarkers present in their body, the LAK-cell activity can be improved with the help of Thymosin alpha. However, further studies were yet to be conducted on individual immunodeficient patients to get a clearer analysis.
Thymosin alpha 1 Research with Hepatitis
Clinical trials were conducted in patients suffering from liver disorders such as hepatitis B & C where Thymosin alpha-1 was tested as a monotherapy as well as in combination with other compounds such as interferon alpha 2a and similar compounds (3).
For hepatitis B, it was noted that when patients were administered with a 1.6mg dose of the peptide twice a week via subcutaneous route, the virological response rate of the patients increased by 40.6%.
For hepatitis C, patients showed improved results when Thymosin alpha-1 peptide was administered as a combination drug therapy along with interferon alpha compounds, rather than the individual peptide administration.
It should be noted that Thymosin alpha was earlier used to treat hepatitis; however, with the discovery of several antiviral agents, Thymosin alpha is no longer prescribed in the treatment of hepatitis disease.
Thymosin alpha 1 Research with Sepsis
In this 2015 study (7), a meta-analysis was conducted where all the relevant clinical trials prior to Dec 12, 2014, were analyzed to understand the use of Thymosin alpha-1 in treating the sepsis chain reaction.
During this time, Thymosin alpha-1 had been established as a promising candidate to treat immunodeficiency, however, it was still unclear whether this medication could be prescribed for sepsis treatment and management.
In this study, 12 controlled trials were evaluated in total. Based on the extracted data and assessment, it was noticed that there was a significant decline in mortality rate amongst patients after the administration of the Thymosin alpha-1. However, it should be noted that all these studies were conducted on an exceedingly small number of patients. While the results showed promising effects, larger, well-designed studies are needed to provide more conclusive analysis and results.
Thymosin alpha 1 Research with HIV
This study (8) consisted of a randomized phase II open-label clinical trial on 20 clinically stable patients. These patients were already undergoing highly active antiretroviral therapy (HAART), along with which Thymosin alpha-1 peptide will also be administered to monitor its impact.
Dose of 3.2 mg Thymosin alpha-1 dose was administered subcutaneously for two times in a week in 13 patients. The remaining seven patients were given placebo. Every 2 weeks, the cell counts of CD4/CD8 cells, CD45 cells and signal joint T-cell receptor circles (sjTREC) levels were monitored.
After 12 weeks, it was noticed that there were no significant changes in the levels of CD4, CD and CD45 levels in both the peptide treated and placebo treated group. However, the sjTREC levels significantly increased in the patients treated with the peptide. These elevated levels of sjTREC in the body could potentially stimulate the immune responses in the body and thereby improve the body’s immune system.
Thymosin alpha 1 Research with Cancer (anti-tumor agent)
In this study (9), the levels of the reactive oxygen species (ROS) were monitored in the body after the administration of Thymosin alpha-1. ROS plays a vital role in various biological processes in our body.
During this study, Thymosin alpha-1 was administered in mice suffering from liver carcinoma. Both the leukomonocytes and HepG2 cells, treated with the peptide, were isolated from the mouse spleens, for the purpose of this study.
Upon analysis, it was noticed that the ROS level was significantly higher in the isolated leuko monocytes whereas it was lower in the HepG2 cells. Also, the peptide increased the levels of the leukomonocytes by enhancing its cell cycle, whereas it delayed the cell cycle for HepG2 cells and thereby reduced their levels in the system.
Thus, this study suggested that Thymosin alpha-1 peptide has potent anti-proliferative property against the malignant cells whereas it exhibits proliferative activity against the leuko monocytes – which is why it can be potentially used as an anti-tumor drug to treat carcinogenic cells in the body.
Thymosin alpha 1 Research with COVID-19
The 2019 coronavirus disease (COVID-19) has caused a global pandemic due to its severe adverse impact to the human body, leading to weakened auto immunity.
In this study(11), 76 severe COVID-19 cases were retrospectively reviewed to understand the benefits and mechanism of Thymosin alpha-1 peptide in COVID-19 treatment. All these 76 cases were from December 2019 to March 2020.
After the study, it was noted that compared to the untreated patients, the patients who received Thymosin alpha-1 treatment showed a significantly reduced mortality rate. The mortality rate in the untreated group was 30% whereas it reduced to 11.11% in the individuals treated with the peptide.
Further analysis showed that the peptide enhanced the number of blood T-cells in the COVID-19 patients. The peptide elevated the levels of CD8+ and CD4+ cells in the patients where the levels of these cells were less than 400/microL and 650 microL respectively. Consequently, the peptide restored lymphocytopenia and reversed the T-cell exhaustion due to which the immune system could be recovered to normal levels.
While further studies are in progress to establish the peptide use, this study showed promising results of the peptide in treatment and management of COVID-19 disease.
Thymosin alpha-1 Side Effects
The common disadvantages or side effects of the Thymosin alpha-1 peptide include the following (12):
- Pain, redness, and discomfort at the site of injection
- Redness and swelling of the hands
- Joint pain
The more serious side effects of the peptide include (11):
- Rashes
- Difficulty in breathing
- Swelling of the face, throat, and tongue
In clinical trials where the peptide was administered in conjunction with the interferon compounds, it resulted in fever, fatigue, nausea, and vomiting in some rare cases (3).
Contraindications
Thymosin alpha-1 peptide is contraindicated in people who suffer from hypersensitivity towards the Thymosin alpha-1 or any ingredients of the injection formulation (3).
Thymosin alpha-1 is not recommended in organ transplant recipients due to the immunomodulatory properties of the peptide (3).
Peptide Doses, Route of Administration and Dosage
Thymosin alpha-1 peptide is a US FDA approved prescription medication that is available in injection form and is mainly administered via subcutaneous route (3). This is also supported by the several clinical studies that have been conducted on human volunteers where this route was chosen for drug administration.
The recommended dose is 0.8 to 6.5 mg twice a week for single dosage, whereas it can be prescribed in 1.6 to 16 mg doses for multiple dosage (3).
Summary
Thymosin alpha-1 is a naturally occurring polypeptide composed of 28 amino acids and secreted from the human thymus gland. It possesses natural abilities to fight immunodeficiency in humans via increasing the T-cell population in the body. The synthetic version of the peptide is also available, commonly known as Thymalfasin.
Various clinical trials have been conducted since its discovery in the 1970s until today which has demonstrated promising results of the peptide in many immunodeficiency ailments including but not limited to cancer, liver disease, HIV, and other autoimmune ailments.
Can Thymosin alpha-1 be Used for COVID-19 Treatment?
The COVID-19 pandemic has caused a severe impact across the globe, and the burning question of the hour has always been about the discovery of its successful medical care.
Multiple clinical studies are ongoing to establish a safe, solid treatment for COVID-19 disease. Preliminary studies (11) have been conducted to examine the use of Thymosin alpha-1 peptide in managing COVID-19 patients and have shown promising results.
Based on the immunomodulatory properties of the peptide and its established use in other autoimmune diseases, Thymosin alpha-1 becomes a very promising candidate in treating this pandemic.
As the studies are still limited, scientists, and researchers will need to explore more in this area to mitigate the catastrophic outcome of this COVID-19 pandemic with the potential use of the Thymosin alpha-1 peptide.
While further studies continue to explore more benefits of the peptide treatment, Thymosin alpha-1 peptide has established its remarkable benefits to human health, making it a successful candidate in the treatment of multiple, severe autoimmune conditions.
References:
1. Immunodeficiency, British Society for Immunology. Published March 2017. https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/immunodeficiency
2. Primary Immune Deficiency Diseases. https://www.niaid.nih.gov/diseases-conditions/primary-immune-deficiency-diseases-pidds
3. Dominari A, Hathaway Iii D, Pandav K, Matos W, Biswas S, Reddy G, Thevuthasan S, Khan MA, Mathew A, Makkar SS, Zaidi M, Fahem MMM, Beas R, Castaneda V, Paul T, Halpern J, Baralt D. Thymosin alpha 1: A comprehensive review of the literature. World J Virol. 2020 Dec 15;9(5):67-78. doi: 10.5501/wjv.v9.i5.67. PMID: 33362999; PMCID: PMC7747025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747025/
4. National Center for Biotechnology Information. “PubChem Compound Summary for CID 16130571, Thymalfasin” PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Thymalfasin
5. Garaci E. Thymosin alpha1: a historical overview. Ann N Y Acad Sci. 2007 Sep;1112:14-20. doi: 10.1196/annals.1415.039. Epub 2007 Jun 13. PMID: 17567941. https://pubmed.ncbi.nlm.nih.gov/17567941/
6. Eckert K, Schmitt M, Garbin F, Wahn U, Maurer HR. Thymosin alpha 1 effects, in vitro, on lymphokine-activated killer cells from patients with primary immunodeficiencies: preliminary results. Int J Immunopharmacol. 1994 Dec;16(12):1019-25. doi: 10.1016/0192-0561(94)90081-7. PMID: 7705963. https://pubmed.ncbi.nlm.nih.gov/7705963/
7. Li C, Bo L, Liu Q, Jin F. Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysis. Int J Infect Dis. 2015 Apr;33:90-6. doi: 10.1016/j.ijid.2014.12.032. Epub 2014 Dec 19. PMID: 25532482. https://pubmed.ncbi.nlm.nih.gov/25532482/
8. Chadwick D, Pido-Lopez J, Pires A, Imami N, Gotch F, Villacian JS, Ravindran S, Paton NI. A pilot study of the safety and efficacy of thymosin alpha 1 in augmenting immune reconstitution in HIV-infected patients with low CD4 counts taking highly active antiretroviral therapy. Clin Exp Immunol. 2003 Dec;134(3):477-81. doi: 10.1111/j.1365-2249.2003.02331.x. PMID: 14632754; PMCID: PMC1808897. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808897/
9. Qin Y, Chen FD, Zhou L, Gong XG, Han QF. Proliferative and anti-proliferative effects of thymosin alpha1 on cells are associated with manipulation of cellular ROS levels. Chem Biol Interact. 2009 Aug 14;180(3):383-8. doi: 10.1016/j.cbi.2009.05.006. Epub 2009 May 12. PMID: 19442654. https://pubmed.ncbi.nlm.nih.gov/19442654/
10. Panatto D, Amicizia D, Lai PL, Camerini R, De Rosa A, Gasparini R. Utility of thymosin alpha-1 (Zadaxin) as a co-adjuvant in influenza vaccines: a review. J Prev Med Hyg. 2011 Sep;52(3):111-5. PMID: 22010537. https://pubmed.ncbi.nlm.nih.gov/22010537/
11. Liu Y, Pan Y, Hu Z, Wu M, Wang C, Feng Z, Mao C, Tan Y, Liu Y, Chen L, Li M, Wang G, Yuan Z, Diao B, Wu Y, Chen Y. Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells. Clin Infect Dis. 2020 Nov 19;71(16):2150-2157. doi: 10.1093/cid/ciaa630. PMID: 32442287; PMCID: PMC7314217. https://pubmed.ncbi.nlm.nih.gov/32442287/
12. Zadaxin (Thymalfasin): Uses, Dosage, Side Effects, Interactions, Warning [Internet]. RxList. 2009. Available from: https://www.rxlist.com/zadaxin-drug.htm
Thymosin Alpha-1 Peptide In The News
Refer to this FDA page regarding Compounded Drug Concerns Related to COVID-19:
https://www.fda.gov/drugs/coronavirus-covid-19-drugs/compounding-activities-covid-19?utm_medium=email&utm_source=govdelivery
Thymosin Alpha-1 Research
For more information on Thymosin Alpha 1 peptide refer to this page.
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