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Additional reports on safety trials are to be found in Thymosin 4: structure, function, and
biological properties supporting current and future clinical applications, David Crockford, Annals
of the New York Academy of Sciences Volume 1194, Thymosins in Health and Disease: 2nd International
Symposium pages 179189, May 2010 where several Phase 2 clinical trials reported safety. No trial has
reported non-safety.
Efficacy
* - In general much of the following derives from, Stem Cell Regulators, edited by
Gerald Litwack, Academic Press, Nov 23, 2011and Thymosin b4: actin-sequestering protein
moonlights to repair injured tissues, Allan L. Goldstein, TRENDS in Molecular Medicine
Vol.11 No.9 September 2005
TB4 is the most abundant actin-sequestering protein in human platelets. Actin functions to form
microfilaments which provide mechanical support to cells, they can act as scaffold for myosin protein
generated muscle contractions and allow for cell motility. Individual subunits (or single units) of
microfilaments are called globular actin (G-actin). G-actin subunits assemble into long filamentous
polymers (multi-units) called F-actin. Two parallel F-actin strands rotate and layer on top of each other
thereby creating the double helix structure of the microfilaments of the cytoskeleton.
TB4 involves itself in this actin filament growth process. It binds to those single subunits called G-actin
and acts as a buffer as more subunits are added to form a multi-unit long chain called F-actin. Before
this making of long-chained F-actin can get going a protein called profilin also binds to G-actin with a
role of exchanging ADP for ATP.
The growth of these long-chained actin filaments is regulated by thymosin and profilin. Thymosin binds
to G-actin to buffer the polymerizing (growing) process, while profilin binds to G-actin and brings about
the actin-bound exchange of ADP for the energy molecule ATP. This energizes these G-actin subunits.
Basically TB4 as a buffer and profilin as a catalyst convert ADP G-actins which normally grow poorly to
ATP G-actins which are ready to bind and grow into long chain F-actin structures. They add energy to the
process. They bring about cellular movement and cell shape change.
Whether TB4's extracellular actions come solely through the receptor mechanism identified by Freeman
is unclear at this time. The Freeman study summarized some of these healing effects as follows.
"TB4 is capable of supporting full-thickness wound healing, acting as a potent angiogenic factor with
anti-inflammatory properties that promote both endothelial and keratinocyte migration into cutaneous
wounds. B-Thymosins evoke a different outcome in corneal wounds, supporting reepithelialization
without inducing angiogenesis, while remaining anti-inflammatory after alkali injury or scrape wounding.
In mice with experimentally induced myocardial infarction, TB4 dramatically improves cardiac function
after intracardial and intravenous injection. TB4 is thought to promote coronary repair by stimulating
migration of myocardiocytes into the infarcted area and by improving myocardial survival via induced
coronary neovascularization."
Subsequent posts in this forum will likely detail the specific aspects of TB4-induced healing. The following
image gives us a quick way to visualize when in the repair process TB4 plays a role.
Biological activities of thymosin 4 defined by active sites in short peptide sequences, Gabriel
Sosne, July 2010 The FASEB Journal vol. 24 no. 7 2144-2151
SUMMARY
It is surprising that a molecule as small as T4 contains so many biological as well as structural
functions. Many of these activities are localized in distinct amino acid-specific peptide sequences (Fig. 5
). At least three different active sites have been identified, including peptide 14, Ac-SDKP, for
antiinflammation and angiogenesis; peptide 1722, LKKTETQ, for actin binding and wound
healing; and peptide 115 for cytotoxicity protection.
While T4 has been described in the cytoplasm and nucleus, it is not clear where these peptides are
localized in the cell at this time (1) . Ac-SDKP appears to be a natural cleavage product (51) ,
but it is not known whether is cleaved from the intact molecule or from smaller fragments. Theactinbinding site LKKTETQ peptide has been found in wound fluid after tryptic cleavage and may
also be a naturally occurring peptide (46) . Peptide 115 has not previously been studied,
and it is not known if it is a naturally occurring fragment or an intermediate in Ac-SDKP
generation.
Thymosin Beta 4 Induces Hair Growth via Stem Cell Migration and
Differentiation, DEBORAH PHILP, Ann. N.Y. Acad. Sci. 1112: 95103 (2007)
ABSTRACT:
Thymosin beta 4 is a small 43-amino-acid molecule that has multiple biological activities, including
promotion of cell migration angiogenesis, cell survival, protease production, and wound healing. We have
found that thymosin beta 4 promotes hair growth in various rat and mice models including a
transgenicthymosin beta 4 overexpressing mouse. We have also determined the mechanism by
which thymosin beta 4 acts to promote hair growth by examining its effects on follicle stem cell growth,
migration, differentiation, and protease production.
TABLE 1. Biological activities of thymosin beta 4
Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in
humans
1.
Temporal expression of growth factors and matrix molecules in healing tendon lesions
1.
Abstract
Overuse tendon injuries are common among elite and recreational athletes. Tendon healing may be enhanced at the cellular level
through the use of exogenous growth factors; however, little is known about the endogenous expression of growth factors in healing
tendon. This study describes the temporal expression of insulin-like growth factor-I (IGF-I), transforming growth factor-1 (TGF-1),
and collagen types I and III in healing tendon lesions. Collagenase-induced lesions were created in the tensile region of the flexor
digitorum superficialis tendon of both forelimbs of 14 horses. Tendons were harvested from euthanatized horses 1, 2, 4, 8 or 24
weeks following injury. Gene expression was evaluated using Northern blot analysis (collagen types I and III), real time PCR (IGF-I
and TGF-1), and in situ hybridization. Protein content was assayed by dye-binding assay (collagen types I and III),
radioimmunoassay (IGF-I), ELISA (TGF-1), and immunohistochemistry. Samples were also processed for differential collagen
typing. DNA and glycosaminoglycan content, and routine H&E staining. Microscopically, lesions progressed from an amorphous,
acellular lesion soon after injury to scar tissue filled with collagen fibers and mature fibroblasts organized along lines of tension. Early
lesions were characterized by immediate increases in expression of growth factors and collagen. Message levels for TGF-1 peaked
early in the wound healing process (1 week), while IGF-I peaked later (4 weeks), as the regenerative phase of healing was
progressing. In the first 2 weeks after lesion induction, tissue levels of IGF-I protein actually decreased approximately 40% compared
to normal tendon. By 4 weeks, these levels had exceeded those of normal tendon and remained elevated through 8 weeks. Message
expression for collagen types I and III increased by 1 week following injury and remained elevated throughout the course of the study.
Collagen type I represented the major type of collagen in healing tendon at all time points of the study. Based on these results, IGF-I,
administered exogenously during the first 2 weeks following injury, may provide a therapeutic advantage by bolstering low
endogenous tissue levels and enhancing the metabolic response of individual tendon fibroblasts