Description

TB-500 Research Studies

The investigation showed that TB500 may be the first agent which can actively recover injured cardiac muscle following heart attack. This is further supported with prior mouse studies in 2004 showing cardiomyocyte migration, survival and repair of myocardial damage. [1] [2]

Filamentous actin (F-actin, or actin) forms polymers that thicken sputum, adversely affecting cystic fibrosis patients. TB500 was studied in a population of CF patients, showing a dose and time-dependent decrease in cohesivity of sputum after administration of TB500 when combined with dornase alfa. The combination therapy showed a 71% improvement in mucociliary transport of mucus, and a 44% improvement in cough transport of mucus. [3]

TB500 is known to stimulate myoblasts and myocytes (muscle generating cells). Mitochondrial RNA levels of TB500 have been shown to increase following muscle injury, helping to regenerate muscle fibers and address inflammation in the injured location. The data support muscle injury causing increased local production of TB500, promoting migration of incoming myoblasts to accelerate skeletal muscle regeneration. [4]

A study completed in 2009 using .01% TB500 w/w eye drops demonstrated increased speed of healing following eye surgery in diabetics. This population was specifically investigated due to well-known healing complications in diabetics, and their predilection for eye issues, specifically diabetic retinopathy. The study showed no serious side effects in any patient, although headache, dizziness and insomnia occurred more in the study group than the control. Of specific interest, human diabetic retinopathic corneas express substantially less endogenous TB500 than a normal cornea, suggesting an inherent deficiency in ability for diabetics to heal following eye injury or surgery. [5]

Similarly, chronic dry-eye patients were treated with TB500 eye drops, and all in the study had improvement in symptoms, with rare and minimal complications. [6]

TB500 was studied in the setting of chronic hepatitis B combined with nonalcoholic fatty liver disease (NAFLD). While TB500 had no correlation with HepB Virus levels nor liver function tests (AST, ALT, TG), there was a negative correlation with inflammation and fibrosis scores – meaning that the lower the level of TB500, the worse the inflammation and fibrosis. This provided preliminary data that TB500 may be beneficial in the setting of certain liver diseases.[7]

A human voluntary safety and tolerance study was performed in 2010, and showed that intravenous (IV) doses from 42mg up to 1260mg daily for 14 days had no treatment related adverse effects, and no evidence of dose related toxicity. [8]

Rhinovirus (a common cold virus) was introduced to healthy volunteers, and blood tests were taken during a five-day period. This showed that serum cortisol rose along with thymosin alpha 1 and TB500 on the fifth day following intentional exposure. Simultaneously, T lymphocytes (CD3+), cytotoxic/suppressor (CD8+), and natural killer (CD16+) cells all rose. This suggests a cooperative effect among systemic and cellular immune response related to thymosin and respiratory virus exposure. [9]

Kidney disease often includes inflammation, fibrosis, and complications from diabetes. TB500 has been studied in mice with and without kidney disease; in healthy mice, levels of TB500 did not affect healthy kidney tissue, but in those with known kidney disease, low levels of TB500 correlated with worsening disease. That is, low levels of natural TB500 accelerated kidney disease. The study suggested that endogenous TB500 levels function to protect the kidney and slow disease progression. [10]

TB500 has been studied specifically in healing of skin and wounds, showing acceleration in healing of skin in burns, diabetic ulcers, elderly subjects, pressure ulcers, stasis ulcers, and epidermolysis wounds, in both animal and human subjects. The study shows improvement in angiogenesis (blood vessel formation), anti-inflammatory activity, and to increase platelet aggregation at wound sites. [11]

References:

1 – Medicine (Baltimore).2016 Dec;95(52):e5763. doi: 10.1097/MD.0000000000005763. The expression of thymosin β4 in chronic hepatitis B combined nonalcoholic fatty liver disease. Liang J1, Cai W, Han T, Jing L, Ma Z, Gao Y.

2 – Nature. 2004 Nov 25;432(7016):466-72. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Bock-Marquette I1, Saxena A, White MD, Dimaio JM, Srivastava D.

3 – Chest. 2006 Nov;130(5):1433-40. Thymosin beta4 sequesters actin in cystic fibrosis sputum and decreases sputum cohesivity in vitro. Rubin BK1, Kater AP, Goldstein AL.

4 – J Biochem. 2011 Jan;149(1):43-8. doi: 10.1093/jb/mvq115. Epub 2010 Sep 29. Muscle injury-induced thymosin β4 acts as a chemoattractant for myoblasts. Tokura Y1, Nakayama Y, Fukada S, Nara N, Yamamoto H, Matsuda R, Hara T.

5 – https://clinicaltrials.gov/show/NCT00598871

6 – Ann N Y Acad Sci. 2010 Apr;1194:199-206. doi: 10.1111/j.1749-6632.2010.05471.x. Treatment of chronic nonhealing neurotrophic corneal epithelial defects with thymosin beta4. Dunn SP1, Heidemann DG, Chow CY, Crockford D, Turjman N, Angel J, Allan CB, Sosne G.

7 – Ann N Y Acad Sci. 2010 Apr;1194:87-96. Thymosin beta4 and cardiac repair. Shrivastava S1, Srivastava D, Olson EN, DiMaio JM, Bock-Marquette I.

8 – Ann N Y Acad Sci. 2010 Apr;1194:223-9. doi: 10.1111/j.1749-6632.2010.05474.x. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ruff D1, Crockford D, Girardi G, Zhang Y.

9 – Lymphokine Res. 1989 Winter;8(4):383-91. Modulation of thymosin alpha 1 and thymosin beta 4 levels and peripheral blood mononuclear cell subsets during experimental rhinovirus colds. Hsia J1, Sztein MB, Naylor PH, Simon GL, Goldstein AL, Hayden FG.

10 – Kidney Int. 2016 Nov;90(5):1056-1070. doi: 10.1016/j.kint.2016.06.032. Epub 2016 Aug 26. Loss of endogenous thymosin β4 accelerates glomerular disease. Vasilopoulou E1, Kolatsi-Joannou M1, Lindenmeyer MT2, White KE3, Robson MG4, Cohen CD2, Sebire NJ1, Riley PR5, Winyard PJ1, Long DA6.

11 – Vitam Horm. 2016;102:251-75. doi: 10.1016/bs.vh.2016.04.005. Epub 2016 May 24.