A modified form of thymosin beta 4 helped heart tissue after heart attack in animals

The science

Original title

PEGylated thymosin β4 is a thiol-site-specific prodrug treating myocardial infarction in vivo.

Authors

Peng H, Chai Y, Gong C et al.

Journal

Bioengineering & translational medicine

Published

Jul 3, 2026

Study type

Study

PMID

42394899 ↗

DOI

10.1002/btm2.70144 ↗

Abstract

Thymosin beta 4 (Tβ4) has been clinically trialed for over 10 years to treat ulcers, dry eye syndrome, and acute myocardial infarction (MI). However, as of now, no Tβ4 drug has been approved. Tβ4, as a small protein drug, has to face druggability challenges such as abundant supply, high purity, verified efficacy and safety, long half-life, and shelf-life. Here, a modified prokaryotic expression system was developed to express recombination Tβ4 (rTβ4), followed by single thiol-site-specific PEGylation of rTβ4, namely PEG-rTβ4 as a prodrug. The identification and thermodynamic properties of PEG-rTβ4 were tested with a matrix-assisted laser desorption-ionization time of flight mass spectrometer, a differential scanning calorimeter, and a thermal gravimetric analyzer. The data showed the superiority of PEG-rTβ4 for treating MI. Long-circulating PEG-rTβ4 significantly relieves myocardial remodeling, restores cardiac function, promotes neoangiogenesis, and inhibits apoptosis via the Akt/Bcl-2/caspase-3 pathway. In summary, PEG-rTβ4 is a better choice for the drug development of this active protein.

Read it on PubMed ↗