Thymosin Beta-4 Research

1. TB-500 and Neurologic Function

Research in rats has found that TB-500 encourages central and peripheral nervous system tissues to undergo repair and remodeling following injury. Though the exact mechanism has yet to be elucidated, the research indicates that TB-500 activates the cells that support neurons. These cells, called oligodendrocytes, keep neurons healthy^[1]. Boosting their activity actually improves blood vessel and neuron growth in brain regions that have been damaged, a significant laboratory result that is reflected in clinically significant improvements in behavior, motor control, and cognitive measurements^[2].

Recent research shows that TB-500 can reduce oxidative stress following spinal cord injury and help transplanted neural stem/progenitor cells (NSPCs) to survive long enough to enhance spinal regeneration^[3]. These findings could make TB-500 and other TB-4 derivatives of great use in treating severe spinal cord injury. TB-550 may offer critical insight into spinal recovery that allows paralyzed individuals to regain use of affected body regions.

2. TB-500 and Blood Vessel Growth

TB-500 and TB-4 are potent stimulators of VEGF expression. VEGF is an important signaling molecule in the growth of capillaries (small blood vessels), which are critical to everything from wound healing to hair growth^[4]. It is thought that the role of TB-500 is more complicated than this, however. Scientists speculate that the peptide likely underpins a number of steps in the process of blood vessel growth include extracellular matrix remodeling, vasculogenesis, angiogenesis, and the transition of more primitive mesenchymal tissue to the specialized endothelial tissue that lines blood vessels. This speculation is valid because loss of TB-4 has been shown to interfere with blood vessel growth and stability while exogenous administration improves capillary formation and the recruitment of pericytes following injury^[4].

3. TB-500 and Hair Growth

The discovery that TB-500 improves hair growth happened by accident. When mice that were genetically deficient in TB-4 were shaved for laboratory experiments, it was observed that their hair grew back much slower than wild-type mice. When these same scientists investigated hair growth in mice that were genetically modified to produce increased levels of TB-4, they found that their hair grew back much faster than normal. Under the microscope, these mice show increased numbers of hair shafts and grouped hair follicles^[5].

4. TB-500 and Antibiotic Synergy

Multi-drug resistance is becoming increasingly common in a number of infections, rendering current therapy ineffective. Unfortunately, there are very few new antibiotics in the pipeline and the process of drug development can take upwards of twenty years on average. A recent study on the effects of TB-4 and its adjuvants, however, provides some hope. Studies of mice suffering from a Pseudomonas aeruginosa infection of the eye have found that TB-4 combined with ciprofloxacin, a standard antibiotic for treating Pseudomonas aeruginosa, increases the effects of the antibiotic, improves healing, reduces inflammation, and promotes faster recovery. The results of just five days of combined therapy showed decreased numbers of colony forming units (CFUs), decreased neutrophil (a type of white blood cell) count, and decreased levels of inflammatory reactive oxygen species^[6]. This the first study to demonstrate that TB-500 and similar peptides might be used to promote and enhance the effects of antibiotics.

A. Number of colony forming units (CFUs) of bacteria after 5 days of treatment. Note that none are detectable when ciprofloxicin is combined with TB-4.
B. Shows number of neutrophils in the corneas of treated mice, an indication of inflammation.
C. Measure of reactive oxygen species in corneas of mice after 5 days of treatment.
D. Nitrate levels from corneal lysates.
Source: PubMed

5. TB-500 and Cardiovascular Health

Two decades of research have shown that TB-4 and its derivatives have a number of beneficial effects in the cardiovascular and renal systems. The exact mechanisms of these positive contributions are not clearly understood, however. Research suggests that the benefits are actually due to several mechanisms. First, TB-500 promotes the growth of collateral blood vessels, which is useful both as a preventative and in restoring function following disease. Second, TB-500 encourage endothelial cell migration and myocycte survival following a heart attack. Finally, it appears that TB-500 works in concert with other natural signaling molecules to reduce inflammation and reduce fibrosis (scar formation)^[7].

Recently, research into hydrogels containing a combination of collagen and TB-4 has shown the peptide promotes angiogenesis and epicardial heart cell migration, thus boosting rates of recovering following ischemia and helping to prevent long-term complications by reducing scarring^[8].

6. TB-500 and Neurodegenerative Diseases

Progress in finding a treatment for neurodegenerative diseases like Alzheimer’s and prion disease has been slow at best. A recent study into the effects of TB-4 on the ability of the immune system to deal with prion protein has shown that the peptide enhances autophagy^[9]. Autophagy is the central nervous system’s primary protective mechanism against neurodegenerative diseases. The ability of TB-4 to enhance this natural immunity is the first progression toward real treatment of these debilitating diseases in a long time.

7. TB-500 Has Wide Application

TB-500 due to its fundamental role in cell structure and function can affect a number of different body tissues. This has resulted in a wide and varied field of research into the effects of this peptide. From treating heart and neurological disease to enhancing the effects of antibiotics, TB-500 is one of the hottest peptides in research today and will likely remain one of the most heavily investigated peptides for the foreseeable future.

Resources

• [1] P. Cheng, F. Kuang, H. Zhang, G. Ju, and J. Wang, “Beneficial effects of thymosin β4 on spinal cord injury in the rat,” Neuropharmacology, vol. 85, pp. 408–416, Oct. 2014. [PubMed]
• [2] M. Chopp and Z. G. Zhang, “Thymosin β4 as a restorative/regenerative therapy for neurological injury and neurodegenerative diseases,” Expert Opin. Biol. Ther., vol. 15 Suppl 1, pp. S9-12, 2015. [PubMed]
• [3] H. Li, Y. Wang, X. Hu, B. Ma, and H. Zhang, “Thymosin beta 4 attenuates oxidative stress-induced injury of spinal cord-derived neural stem/progenitor cells through the TLR4/MyD88 pathway,” Gene, vol. 707, pp. 136–142, May 2019. [PubMed]
• [4] K. N. Dubé and N. Smart, “Thymosin β4 and the vasculature: multiple roles in development, repair and protection against disease,” Expert Opin. Biol. Ther., vol. 18, no. sup1, pp. 131–139, 2018. [PubMed]
• [5] D. Philp, S. St-Surin, H.-J. Cha, H.-S. Moon, H. K. Kleinman, and M. Elkin, “Thymosin beta 4 induces hair growth via stem cell migration and differentiation,” Ann. N. Y. Acad. Sci., vol. 1112, pp. 95–103, Sep. 2007. [PubMed]
• [6] T. W. Carion et al., “Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy Improves Pseudomonas aeruginosa-Induced Keratitis,” Cells, vol. 7, no. 10, Sep. 2018. [PubMed]
• [7] K. M. Kassem, S. Vaid, H. Peng, S. Sarkar, and N.-E. Rhaleb, “Tβ4-Ac-SDKP pathway: Any relevance for the cardiovascular system?,” Can. J. Physiol. Pharmacol., pp. 1–11, Mar. 2019. [PubMed]
• [8] A. D. Shaghiera, P. Widiyanti, and H. Yusuf, “Synthesis and Characterization of Injectable Hydrogels with Varying Collagen–Chitosan–Thymosin β4 Composition for Myocardial Infarction Therapy,” J. Funct. Biomater., vol. 9, no. 2, Mar. 2018. [PubMed]
• [9] H.-J. Han, S. Kim, and J. Kwon, “Thymosin beta 4-Induced Autophagy Increases Cholinergic Signaling in PrP (106-126)-Treated HT22 Cells,” Neurotox. Res., Dec. 2018. [PubMed]