TB-500 (thymosin beta-4, TB4) is a synthetic version of a naturally occurring 43–amino-acid peptide found in high concentrations in platelets, wound fluid, and many tissues. It’s being investigated for tissue repair, immune modulation, and cell regeneration. Preclinical and early clinical work suggest roles in skin and connective-tissue repair, reduced inflammation, hair growth, and potential cardioprotective and neuroprotective effects.
Key Functions & Benefits (research/early clinical)
- Enhanced wound healing: Supports re-epithelialization, collagen deposition, wound contraction, and tissue remodeling in skin, muscle, ligaments, and tendons.
- Anti-inflammatory activity: Down-modulates inflammatory cytokines and oxidative damage, potentially speeding recovery.
- Connective tissue repair: Promotes tendon/ligament and skeletal muscle healing; improves flexibility.
- Angiogenesis: Stimulates new blood vessel formation to improve oxygen/nutrient delivery to injured tissue.
- Stem-cell activation: Mobilizes progenitor/stem cells in damaged tissues and hair follicles; associated with hair growth in animal studies.
- Cardiovascular support: Experimental models suggest cardiac protection/regeneration after injury.
- Neurologic applications (preclinical): Signals neuroprotective/neurorestorative effects after brain/spinal cord injury.
- Ocular surface repair: Early clinical work in corneal injury and dry eye.
- Airway mucus rheology (CF): In vitro/early work shows reduced sputum cohesivity with actin sequestration.
Regulatory note: TB-500 remains investigational; not approved for therapeutic use in many jurisdictions and prohibited by WADA. Use is limited to research in appropriate settings.
How TB-500 Works
- Actin regulation (LKKTETQ motif): TB-500 binds/sequesters G-actin, facilitating cell migration, proliferation, and cytoskeletal remodeling—key to wound closure, angiogenesis, and myofiber repair.
- Systemic reach: Low molecular weight and diffusibility allow distribution to distant injury sites.
- Pro-angiogenic signaling: Upregulates pathways that promote endothelial migration and neovascularization.
- Immunomodulation/anti-oxidation: Dampens inflammatory signaling and oxidative stress in several models.
Research & Applications (selected highlights)
Skin & wound healing
- Acute wounds: Animal studies show ~41% faster closure with topical or IP TB-500, with enhanced re-epithelialization and collagen deposition.
- Chronic wounds: Early trials/series in diabetic/pressure ulcers indicate accelerated healing via stem-cell migration and inflammation reduction. [11][12]
Musculoskeletal
- Skeletal muscle: Injury increases local TB4 expression; exogenous TB-500 promotes myoblast chemotaxis and myofiber regeneration. [4]
- Fracture repair: Mice treated with TB-500 had 41% higher peak force to failure, 25% greater stiffness, and improved callus quality vs. controls. [13]
Cardiovascular & pulmonary
- Cardiac repair: In mice, TB4/TB-500 activated integrin-linked kinase, enhanced cardiomyocyte migration/survival, and reduced cell death post-MI; improved neovascularization. [1][2]
- Cystic fibrosis sputum: TB-500 reduced sputum cohesivity (dose/time-dependent) and, with dornase alfa, improved mucociliary (+71%) and cough transport (+44%) in vitro. [3]
Neurologic
- TBI: Demonstrated neuroprotective and neurorestorative effects—enhanced perfusion, neurogenesis, and connectivity—in rodent models. [15]
- Spinal cord injury: Reduced cytokines and scar size; increased myelin proteins (+57.8%) with improved locomotion in rats. [14]
- Multiple sclerosis model: Increased oligodendrogenesis and remyelination with functional improvement. [16]
Ocular surface
- Corneal healing & dry eye: 0.01% TB-500 eye drops improved post-surgical healing in diabetics and reduced symptoms in chronic dry-eye cohorts with minimal adverse effects. [5][6]
Liver & kidney signals
- NAFLD/HBV cohort: Lower endogenous TB4 correlated with worse inflammation/fibrosis (hypothesis-generating). [7]
- Kidney disease: Loss of endogenous TB4 accelerated glomerular injury in models; physiologic levels appeared protective. [10]
Immune & safety
- Viral challenge: During rhinovirus colds, endogenous TB4 rose alongside thymosin α1 and cytotoxic/NK cell activity, suggesting coordinated immune response. [9]
- Human safety/tolerability: IV doses 42–1260 mg daily ×14 days in healthy volunteers showed no dose-related toxicity or treatment-related AEs. (Study drug: thymosin β-4.) [8]
Handling, Reconstitution & Storage (research use)
- Form: Lyophilized powder.
- Reconstitution: Use bacteriostatic 0.9% sodium chloride for research protocols.
- Storage (unreconstituted): Room temperature, dry, protected from light.
- After first use: Refrigerate; typical research guidance suggests up to ~8 days. (Follow your protocol/IRB/manufacturer.)
Administration (research contexts only)
- Common routes: Subcutaneous preferred; intramuscular used in some protocols.
- Exploratory dosing: Literature and grey-literature protocols range widely (e.g., 5–20 mg/week, divided 2–3 injections/week, then lower “maintenance”). Dosing is not standardized—must follow your approved research protocol.
Side Effects & Considerations
- Generally well-tolerated in reported studies.
- Possible but uncommon: transient nausea, fatigue, flu-like feelings, lightheadedness at injection.
- Athletic use: Banned by WADA.
- Clinical status: Investigational; not a substitute for medical care. Use under appropriate research governance.
Summary
TB-500 (thymosin beta-4) is a widely expressed, actin-modulating peptide under active investigation for wound healing, tissue regeneration, anti-inflammatory effects, and vascular/neurologic repair. Preclinical and early clinical findings are promising across dermatologic, musculoskeletal, cardiac, neurologic, ocular, and mucosal applications. Robust, controlled human trials are still needed to define indications, dosing, and long-term safety. For researchers, adhere strictly to protocol, regulatory frameworks, and ethical guidelines.
References
- Ann N Y Acad Sci. 2010;1194:87-96. Thymosin β4 and cardiac repair.
- Nature. 2004;432(7016):466-72. Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration/survival/repair.
- Chest. 2006;130(5):1433-40. TB4 sequesters actin and decreases sputum cohesivity in vitro.
- J Biochem. 2011;149(1):43-8. Muscle-injury-induced TB4 chemoattracts myoblasts.
- ClinicalTrials.gov: NCT00598871 (post-op corneal healing, diabetics).
- Ann N Y Acad Sci. 2010;1194:199-206. Chronic non-healing neurotrophic corneal epithelial defects.
- Medicine (Baltimore). 2016;95(52):e5763. TB4 expression in chronic hepatitis B with NAFLD.
- Ann N Y Acad Sci. 2010;1194:223-9. Randomized, placebo-controlled single/multiple-dose IV TB4 in healthy volunteers.
- Lymphokine Res. 1989;8(4):383-91. Thymosin α1/β4 modulation during experimental rhinovirus colds.
- Kidney Int. 2016;90(5):1056-1070. Loss of endogenous TB4 accelerates glomerular disease.
- Vitam Horm. 2016;102:251-75. TB4 promotes dermal healing (review).
- Expert Opin Biol Ther. 2015;15(S1):S139-45. Advances in basic/clinical TB4 applications (review).
- J Orthop Res. 2014;32(10):1277-82. TB4 enhances fracture healing in mice.
- Neuropharmacology. 2014;85:408-16. Benefits in rat spinal cord injury.
- Ann N Y Acad Sci. 2012;1270:51-8. Neuroprotective/restorative effects after experimental TBI.
- Neurobiol Dis. 2016;88:85-95. TB4 promotes oligodendrogenesis/remyelination in demyelinating CNS.
