01 Identity
| Common name | Thymosin β4 (Tβ4, TB4) |
|---|---|
| Gene | TMSB4X |
| Class | Naturally occurring 43-amino-acid peptide; the major intracellular G-actin-sequestering molecule |
| Structure | N-terminally acetylated; MW ≈ 4,982 Da |
| PubChem CID | 16133418 |
| Clinical formulations | RGN-259 (ophthalmic); RGN-137 (topical dermal); RGN-352 (injectable) |
Endogenous and near-ubiquitous in human cells, where it regulates actin dynamics. Its therapeutic interest comes from that role in cell migration and repair. Unlike most peptides marketed for "healing," Tβ4 has a genuine pharmaceutical development history, which is what gives this page more human evidence to grade than its preclinical-only neighbours.
02 Regulatory status
Thymosin β4 holds no marketing authorisation anywhere. Its most advanced formulation, the RGN-259 ophthalmic solution, completed late-stage trials and carries orphan-drug designation for neurotrophic keratopathy in the US, but has not been approved for marketing.
WADA prohibits thymosin β4 (class S2). In the US it is handled through compounding channels and subject to the FDA's compounding-substance review. No controlled-substance scheduling. Confirm specifics against FDA and WADA documents.
03 Mechanism of action
Tβ4 is the principal G-actin-sequestering peptide in eukaryotic cells, regulating the polymerisation that drives cell migration. Reported downstream effects (cell/animal studies) include cell migration and angiogenesis, anti-inflammatory and anti-fibrotic activity, and, in a widely cited mouse study (Bock-Marquette et al., Nature 2004), integrin-linked-kinase activation with cardioprotection after experimental infarction.
A short C-terminal (actin-binding) region carries much of the activity, and is the basis for the marketed fragment in the TB-500 monograph. The mechanism is among the better-characterised in this class, with contributions from multiple independent laboratories.
04 Pharmacokinetics / pharmacodynamics
A Phase 1 intravenous study in 40 healthy volunteers (single ascending doses, then 14 days daily) reported no dose-limiting toxicities, establishing short-term systemic tolerability of the IV protein. For the topical formulations, local delivery is the relevant question, addressed by the trials below. Long-term systemic PK is not established.
05 Evidence by endpoint
Unlike the rest of this group, Tβ4 has completed human trials. They sit in local indications, and the furthest-developed of them returned mixed results.
5.1 — Ophthalmic surface disease — dry eye & neurotrophic keratopathy (topical, RGN-259)
The best-developed evidence, by the ocular route. A randomised Phase 2 in dry eye (~72 subjects; Sosne et al., Cornea 2015) reduced corneal staining and discomfort versus placebo. The Phase 3 dry-eye programme was mixed — co-primary endpoints not consistently met. A separate neurotrophic keratopathy programme was more encouraging and underlies the orphan designation.
Human topical/local only (Phase 3 dry-eye mixed)5.2 — Dermal wound healing (topical, RGN-137)
Studied for chronic wounds — a double-blind placebo-controlled Phase 2 in venous stasis/pressure ulcers (Guarnera et al., 2010; ~73 patients) reported acceptable safety and partial benefit at the higher concentration — and in epidermolysis bullosa.
Human topical/local only5.3 — Cardiac repair (systemic, RGN-352)
Notable preclinical cardiac data (mouse, pig). In humans, a small pilot transplanted Tβ4-treated endothelial progenitor cells into 10 post-heart-attack patients (5/5), reporting improved cardiac function; RGN-352 is described as Phase-2-ready.
Preclinical + small human pilot5.4 — Neuroprotection (stroke, TBI, neurological repair)
Reported in animal models of stroke and CNS injury.
Preclinical / mechanistic5.5 — Mechanism (actin sequestration, angiogenesis, anti-fibrosis)
Well-characterised across multiple laboratories in cells and animals.
Mechanistic / preclinical06 Safety and adverse events
Thymosin β4 has more human safety data than most peptides in this group, though still limited. The Phase 1 IV study reported short-term tolerability; topical ophthalmic/dermal trials reported acceptable local safety. This is short-term, formulation-specific data; long-term human safety is not established, and systemic dosing beyond the studied protocols is uncharacterised.
07 Evidence summary
| Endpoint (formulation / route) | Grade |
|---|---|
| Dry eye / keratopathy — RGN-259, topical | Human topical/local only |
| Dermal wounds — RGN-137, topical | Human topical/local only |
| Cardiac repair — RGN-352, systemic | Preclinical + pilot |
| Neuroprotection — systemic | Preclinical / mechanistic |
| Long-term human safety | No data |
08 References
- Bock-Marquette I, et al. Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432:466–472.
- Malinda KM, et al. Thymosin β4 accelerates wound healing. J Invest Dermatol. 1999;113(3):364–368.Confirm pagination
- Sosne G, et al. Thymosin β4 significantly improves signs and symptoms of severe dry eye in a Phase 2 randomized trial. Cornea. 2015;34(5).PMID 26056426
- Guarnera G, et al. Topical thymosin β4 for chronic wounds — double-blind placebo-controlled Phase 2. 2010.NCT00382174 · confirm citation
- Ruff D, et al. Phase 1 IV thymosin β4 safety study (40 healthy volunteers). 2010.Confirm citation
- RegeneRx — pilot trial of Tβ4-treated EPCs in STEMI patients (2016); RGN-259 / RGN-137 / RGN-352 programmes.Company / clinical source
- WADA — Prohibited List, class S2.Confirm current listing