What the Research Says

To make the picture honest, this page is split by molecule. First come the studies of thymosin beta-4, then the much smaller body of work on TB-500 itself.

Thymosin Beta-4 in Animals

• Skin wounds in rats (J Invest Dermatol, 1999): applied to the skin or given by injection, thymosin beta-4 increased the regrowth of skin over full-thickness wounds by 42% at day 4 and up to 61% at day 7, compared with saline. It also increased keratinocyte migration two- to threefold in the lab.
• Heart injury in mice (Nature, 2004): after a coronary artery was tied off, treated mice kept more heart muscle cells alive and had better heart function. The protein worked through proteins called ILK and Akt.
• Heart repair cells (Nature, 2007): in adult mouse hearts, thymosin beta-4 woke up dormant cells in the outer layer and helped them form new blood vessel cells.

Thymosin Beta-4 in People

• Safety in volunteers (2010): 40 healthy adults received intravenous thymosin beta-4 or placebo, at single doses from 42 to 1,260 mg and then daily for 14 days. The study reported no dose-limiting toxicity and no serious adverse events.
• Venous leg ulcers (2010): a placebo-controlled Phase 2 trial with 73 patients in Italy and Poland tested a topical gel. Safety was similar to placebo. The authors reported a possible speeding of healing at one dose, with complete closure in about a quarter of patients within three months.
• Severe dry eye (Cornea, 2015): a Phase 2 trial with nine patients found less discomfort and less corneal damage with RGN-259 eye drops than with vehicle drops.
• Neurotrophic keratopathy (Int J Mol Sci, 2022): in a Phase 3 trial with 18 patients, a corneal wound healed completely after four weeks in 6 of 10 on RGN-259 and 1 of 8 on placebo. The difference in this main measure was not statistically significant, although some secondary measures were.

These trials were small, and several were run or funded by the companies developing the product. Promising signals have not yet been turned into an approved medicine.

TB-500 Itself

• Detection in horses (J Chromatogr A, 2012): the fragment and its breakdown products could be found in horse plasma and urine after a single dose. The study was about testing, not about effects.
• Metabolism and cell tests (J Chromatogr B, 2024): TB-500 was broken down quickly, and in fibroblast tests only its fragment Ac-LKKTE improved wound closure.

We found no published controlled study of TB-500 in humans. Claims about its effects in people therefore rest on studies of a different, much larger molecule.

Open Questions

• Does the seven-amino-acid fragment reproduce any of the effects of the full protein in living animals?
• What happens with repeated or long-term exposure?
• Could stimulating cell migration and new blood vessels have unwanted effects, for example on existing tumours?
• How consistent is the quality of material sold under the TB-500 name?

References

1. Low TL, Goldstein AL. Chemical characterization of thymosin beta 4. J Biol Chem. 1982;257:1000-1006. PMID 7054160
2. Safer D, Elzinga M, Nachmias VT. Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable. J Biol Chem. 1991;266:4029-4032. PMID 1999398
3. Malinda KM, et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113:364-368. PMID 10469335
4. Bock-Marquette I, et al. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432:466-472. PMID 15565145
5. Smart N, et al. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2007;445:177-182. PMID 17108969
6. Ruff D, et al. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ann N Y Acad Sci. 2010;1194:223-229. PMID 20536472
7. Guarnera G, et al. The effect of thymosin treatment of venous ulcers. Ann N Y Acad Sci. 2010;1194:207-212. PMID 20536470
8. Treadwell T, et al. The regenerative peptide thymosin β4 accelerates the rate of dermal healing in preclinical animal models and in patients. Ann N Y Acad Sci. 2012;1270:37-44. PMID 23050815
9. Ho EN, et al. Doping control analysis of TB-500, a synthetic version of an active region of thymosin β4, in equine urine and plasma. J Chromatogr A. 2012;1265:57-69. PMID 23084823
10. Davison G, Brown S. The potential use and abuse of thymosin β-4 in sport and exercise science. J Sports Sci. 2013;31:917-918. PMID 23421910
11. Sosne G, Dunn SP, Kim C. Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. Cornea. 2015;34:491-496. PMID 25826322
12. Sosne G, et al. 0.1% RGN-259 (thymosin ß4) ophthalmic solution promotes healing and improves comfort in neurotrophic keratopathy patients in a randomized, placebo-controlled, double-masked phase III clinical trial. Int J Mol Sci. 2022;24:554. PMID 36613994
13. Rahaman KA, et al. Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS. J Chromatogr B. 2024;1235:124033. PMID 38382158
14. Delcourt V, et al. Equine doping controls of thymosin β4: a population study and strategy for misuse detection. Drug Test Anal. 2025. PMID 39314109