While significant progress has been made in treating multiple sclerosis (MS) with the development of immunomodulatory and anti-inflammatory therapies, regenerative therapy would provide MS patients with a new tool to treat their disease. Research indicates that thymosin beta 4 (Tβ4) can potentially treat MS in people at both early and late stages, possibly alone or in combination with existing therapies. Tβ4 has also improved functional outcomes in a rodent model of embolic stroke (1) and trauma (2).

Tβ4 increased myelinated axons and angiogenesis in these studies in the ischemic boundary and augmented re-myelination. There was also an increase in oligodendrocyte progenitor cells and myelinating oligodendrocytes. The repair process after stroke and trauma parallels that in the heart after myocardial infarction, where Tβ4 promotes cardiomyocyte survival and improved cardiac function by recruiting stem/progenitor cells and reducing inflammation and scar production (3). Tβ4 has the potential to control inflammatory processes in the brain, which opens avenues for new therapeutic applications to a range of neurodegenerative conditions (4).

References

1. Morris DC, Chopp M, Zhang L, et al. Thymosin Tbeta4 improves functional neurological outcome in a rat model of embolic stroke. Neuroscience 2010;169:674-82.

2. Xiong Y, Mahmood A, Meng Y, et al. Treatment of traumatic brain injury with thymosin beta4 in rats. J Neurosurg 2011;114:102-15.

3. Bjørklund G, Dadar M, Aaseth J, Chirumbolo S. Thymosin β4: A Multi-Faceted Tissue Repair Stimulating Protein in Heart Injury. Curr Med Chem 2020;27:6294-305.

4. Pardon MC. Share Anti-inflammatory potential of thymosin β4 in the central nervous system: implications for progressive neurodegenerative diseases. Expert Opin Biol Ther 2018;18(sup1):165-9. doi: 10.1080/14712598.2018.1486817.

Dry eye syndrome (DES) affects more than 30 million people in the US alone. DES is characterized by ocular surface inflammation. Consequently, patients can suffer from burning, irritation, severe discomfort, foreign body sensation, and blurry and decreased vision. Thymosin beta 4 (Tβ4) significantly improves signs and symptoms of dry eye without any toxic effects.

Current wound healing and anti-inflammatory treatment options for the cornea are limited, and some of the agents used may cause significant complications and side effects. Tβ4 promotes corneal epithelial cell migration, decreases the expression of corneal epithelial cytokines and chemokines (IL-1β and IL-8, respectively), and inhibits corneal PMN infiltration and adhesion to endothelium. Björklund Pharma AS focuses on Tβ4 product development.

PubMed articles: https://bit.ly/3Rw9BxC

Thymosin beta 4 (Tβ4) may, due to its fibrinolysis and other activities, be useful in treating COVID-19 patients. Tβ4 prevents actin from binding to fibrin, a major blood clot component. Increased fibrinolysis may be achieved by increasing ACE or administering Tβ4 (1).

Fibrinolysis is fibrin breakdown in blood clots. In patients with COVID-19, blood clots have led to extensive morbidity and death. Elevated bradykinin levels in multiple tissues and systems may cause increased vascular dilation, vascular permeability, and hypotension. High bradykinin levels induce pain and cause blood vessels to expand and become leaky, leading to swelling and inflammation of the surrounding tissue. In COVID-19 patients, bradykinin storm induces fluid leakage into the lungs, elevates hyaluronic acid release, impacts oxygen uptake and carbon dioxide release, and causes many severe symptoms (1).

Women have two X chromosomes while men only have one. The Tβ4 gene resides on the X chromosome, which is interesting since men are 2.4 times more likely than women to die from COVID-19. Higher Tβ4 levels may explain why women have a lower incidence of COVID-19-induced mortality than men. If this is correct, pharmacological Tβ4 administration to COVID-19 patients may significantly reduce morbidity and improve survival (1).

Tβ4 not only down-regulates inflammatory chemokines, cytokines, and pro-inflammatory processes, such as bradykinin storm, but also increases fibrinolysis and accelerates wound repair in organs often affected by COVID-19, including the heart, lungs, and kidneys. The Tβ4 levels decrease significantly in blood, tears, and saliva by age (1). Therefore, treatment with Tβ4, which dampens bradykinin storm, may successfully treat COVID-19, particularly in elderly and vulnerable patients.

References

1. Garvin MR, Alvarez C, Miller JI, Prates ET, Walker AM, Amos BK, Mast AE, Justice A, Aronow B, Jacobson D. A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm. Elife 2020;9:e59177. doi: 10.7554/eLife.59177.