Thymosin Beta-4

In simple words

Thymosin beta-4 is a natural 43-amino-acid protein that helps cells move to the site of injury. It is studied for tissue healing: repair of heart muscle and blood vessels, and in eye drops for severe dry eye.

What this molecule is

43 amino acids: Ac-Ser-Asp-Lys-Pro-Asp-Met-Ala-Glu-Ile-Glu-Lys-Phe-Asp-Lys-Ser-Lys-Leu-Lys-Lys-Thr-Glu-Thr-Gln-Glu-Lys-Asn-Pro-Leu-Pro-Ser-Lys-Glu-Thr-Ile-Glu-Gln-Glu-Lys-Gln-Ala-Gly-Glu-Ser. ~4921 Da. Full-length protein.

Why it is studied

Phase I IV safety study (n=54+30, J Cell Mol Med 2021). Phase II RCT — RGN-259 (0.1% eye drops): severe dry eye (Cornea 2015). The first molecule shown to simultaneously regenerate myocardium and blood vessels (Ann NY Acad Sci 2010). Prohibited by WADA (S2).

How it works

G-actin binding → ↑cell migration to the injury zone. ↑VEGF/Ang-1 → ↑angiogenesis. ↓NF-κB/TNF-α/IL-1β → anti-inflammatory effect. Cardiac: activation of c-kit+ epicardial progenitors → neovasculogenesis + cardiomyocyte regeneration. Eye: ↓inflammation + ↑corneal epithelialization.

Doses used in studies

Studies used: for dry eye — RGN-259 0.1% drops twice daily; in Phase I (systemic) — 0.05–25 mcg/kg IV as a single dose. In researchers' practice, 750 mcg – 2 mg SC twice weekly for a course of 4–12 weeks has been described.

Combined with in studies

• BPC-157 — complementary pathways: Tβ4 = actin/angiogenesis, BPC = NO/GI tract
• GHK-Cu — skin + wounds
• Sermorelin — GH axis + regeneration

Level of evidence

Level A-B Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. Phase I + Phase II RCTs in humans.

Important to know

⚠️ TB-500 (LKKTETQ fragment) ≠ Tβ4 — all clinical data concern the full-length molecule. WADA S2 prohibition (2022). Phase III not completed. Research only (not for the commercially available TB-500).

Studies in PubMed

1. Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. (Cornea, 2015)
2. A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers. (J Cell Mol Med, 2021)
3. Thymosin beta4 and cardiac repair. (Ann N Y Acad Sci, 2010)
4. Thymosin β4: A Multi-Faceted Tissue Repair Stimulating Protein in Heart Injury. (Curr Med Chem, 2020)
5. Thymosin beta 4 and the eye: the journey from bench to bedside. (Expert Opin Biol Ther, 2018)
6. Utilizing Developmentally Essential Secreted Peptides Such as Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State-New Directions in Anti-Aging Regenerative Therapies. (Cells, 2021)