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Tb52.5

TB-500 Research

Mostly mechanism / observationalLimited safety

13 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most TB-500 studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from mixed-quality randomised trials published 1990–2022 with a typical study size of 18 participants.

Based on 13 studies · 2 RCTs · 701 total participants

Confidence

Low

By outcome

Vision & eye health
Mostly mechanism / observational3 studies
Cardiac repair & heart
Too few graded studies2 studies
Wound & ulcer healing
Too few graded studies1 study
Hair & nails
Too few graded studies1 study
Tumor biology & cancer risk
Too few graded studies1 study
Safety profile
Too few graded studies1 study

Steady research

2 studies in the last 5 years

199020062022

1Review2012

Thymosin β4 binds to actin and promotes cell migration, including the mobilization, migration, and differentiation of stem/progenitor cells, which form new blood vessels and regenerate the tissue.

Goldstein AL, Hannappel E, Sosne G, Kleinman HK. · Expert Opin Biol Ther (2012)

Review of thymosin β-4 (Tβ4) as a naturally occurring repair/regeneration peptide released after injury
Tβ4 sequesters G-actin, promotes cell migration and angiogenesis, and reduces inflammation and scarring
Surveys proposed therapeutic uses in skin, eye, heart and brain — largely preclinical with early clinical work

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2Review2003

Only the effects of thymosin beta 4 on the actin cytoskeleton have an explanation based on identified molecular interactions.

Bubb MR. · Vitam Horm (2003)

Review of the molecular interactions of Tβ4, a ~5-kDa actin-monomer-sequestering protein
Notes Tβ4 also acts as an anti-inflammatory agent and inhibitor of bone-marrow stem-cell proliferation
Emphasizes that, apart from actin sequestration, most attributed functions lack a defined molecular mechanism

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3Review2016

Tβ4 also accelerated the rate of repair in phase 2 trials with patients having pressure ulcers, stasis ulcers, and epidermolysis bullosa wounds.

Kleinman HK, Sosne G. · Vitam Horm (2016)

Review of Tβ4 in dermal wound repair, with angiogenic and anti-inflammatory activity
Tβ4 accelerated healing across multiple preclinical models, including diabetic and aged animals and burns
Reports Phase 2 trials in pressure ulcers, stasis ulcers and epidermolysis bullosa where Tβ4 accelerated repair

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4Review2016

Treatment with thymosin beta 4 (Tβ4) reduces infarct volume and preserves cardiac function in preclinical models of cardiac ischemic injury.

Pipes GT, Yang J. · Vitam Horm (2016)

Review of Tβ4 cardioprotection in preclinical models of cardiac ischemic injury
Reduces infarct size with additional antifibrotic and proangiogenic effects
Effects attributed to SRF-MRTF-G-actin signaling and pleiotropic pathway interactions

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5In Vitro1990

AcSDKP a new regulator of the hematopoietic system can be generated from thymosin beta 4 by a one-step enzymatic cleavage in vitro and in vivo.

Grillon C, Rieger K, Bakala J, Schott D, Morgat JL, Hannappel E, Voelter W, Lenfant M. · FEBS Lett (1990)

In-vitro / in-vivo demonstration that the regulatory tetrapeptide AcSDKP is generated from Tβ4 by enzymatic cleavage
Both Tβ4 and AcSDKP were detected in bone-marrow cells
Identifies a Tβ4-derived signaling product relevant to hematopoiesis and tissue regulation

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6In Vitro1993

The increase in F-actin is correlated with a corresponding decrease in the complex of G-actin with T beta 4.

Nachmias VT, Cassimeris L, Golla R, Safer D. · Eur J Cell Biol (1993)

Mechanistic study of the Tβ4–G-actin complex in thrombin-activated human platelets
Actin polymerization on platelet activation tracks loss of the Tβ4–G-actin complex
Supports the model of Tβ4 as a dynamic buffer of polymerizable actin

7Review2018

Phase 3 clinical trials using Tβ4 to treat dry eye and neurotrophic keratopathy are currently ongoing.

Sosne G. · Expert Opin Biol Ther (2018)

Narrative review of Tβ4 in ocular surface repair, from basic discovery to clinical translation
Phase 3 trials of Tβ4 (RGN-259) for dry eye and neurotrophic keratopathy were underway
Frames the strongest human-trial evidence for any Tβ4 indication — ophthalmic, not musculoskeletal

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8Observationaln=657 · large study2017

Plasma TB4 is elevated in women with HFpEF and has prognostic information.

Drum CL, Tan WKY, Chan SP, Pakkiri LS, Chong JPC, Liew OW, Ng TP, Ling LH, Sim D, Leong KTG, Yeo PSD, Ong HY, Jaufeerally F, Wong RCC, Chai P, Low AF, Lund M, Devlin G, Troughton R, Cameron VA, Lam CSP, Richards AM. · J Am Heart Assoc (2017)

Human biomarker study measuring circulating TB4 by mass spectrometry in HFpEF (n=219), HFrEF (n=219) and controls (n=219)
Plasma TB4 elevated specifically in women with HFpEF, carrying prognostic information
Studies endogenous, circulating TB4 — not administered TB-500 — as a biomarker

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9Animal2015

Hair re-growth was faster in Tβ4-overexpressing mice, but slower in knockout mice.

Gao X, Liang H, Hou F, Zhang Z, Nuo M, Guo X, Liu D. · PLoS One (2015)

Transgenic mouse study: epidermal Tβ4 overexpression accelerated hair regrowth; global knockout slowed it
Tβ4 upregulated VEGF and modulated P38/ERK/AKT signaling, linking it to angiogenesis-driven follicle growth
An animal model demonstrating the cell-migration / angiogenesis process attributed to Tβ4

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10RCTn=18 · very small study2022

Complete healing occurred after 4 weeks in 6 of the 10 RGN-259-treated subjects and in 1 of the 8 placebo-treated subjects (p = 0.0656), indicating a strong efficacy trend.

Sosne G, Kleinman HK, Springs C, Gross RH, Sung J, Kang S. · Int J Mol Sci (2022)

Randomized, placebo-controlled, double-masked Phase 3 trial of 0.1% RGN-259 (pharmaceutical thymosin β-4) eye drops for persistent epithelial defects in Stage 2-3 neurotrophic keratopathy
Complete healing at 4 weeks in 6/10 treated vs 1/8 placebo (p = 0.0656, trend); significant healing by day 43 (p = 0.0359) with no recurrence in the treated group
Treated subjects had significant improvements in ocular discomfort, foreign-body sensation and dryness; no significant adverse effects

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11In Vitro2007

TB4 induces tumor metastasis and paclitaxel resistance, which is the most significant obstacle to successful therapy in tumors.

Moon EY, Song JH, Yang KH. · Oncol Res (2007)

Cell-model study: TB4 peptide treatment / overexpression increased tumor-cell survival and reduced paclitaxel-induced caspase-3 activation
Silencing TB4 (siRNA) reduced viability and increased caspase-3 activity
Links TB4 to tumor metastasis and chemoresistance in HeLa and gastric tumor cell lines

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12RCTn=9 · very small study2015

At day 56, the RGN-259-treated group (12 eyes) had 35.1% reduction of ocular discomfort compared with vehicle control (6 eyes) (P = 0.0141), and 59.1% reduction of total corneal fluorescein staining compared with vehicle control (P = 0.0108).

Sosne G, Dunn SP, Kim C. · Cornea (2015)

Small multicenter, randomized, double-masked, placebo-controlled Phase 2 trial of 0.1% RGN-259 (thymosin β-4) eye drops in 9 patients with severe dry eye
Significant reductions in ocular discomfort (OSDI) and corneal fluorescein staining vs vehicle at multiple time points, persisting 28 days post-treatment
RGN-259 was safe and well tolerated and met key efficacy objectives (NCT01393132)

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13Observationaln=17 · very small study2021

This small study suggests that intra-articular injection of BPC-157 helps with multiple types of knee pain.

Lee E, Padgett B. · Altern Ther Health Med (2021)

Retrospective chart review of 17 patients given intra-articular BPC 157 (alone or with thymosin-beta-4) for knee pain; 16 followed up by phone
11 of 12 patients (91.6%) who received BPC 157 alone reported significant improvement; 14 of 16 overall reported relief
Uncontrolled and unblinded, self-reported outcomes, no objective imaging or function measures — the authors call for future studies

View in Research Library

TB-500 Research

Mostly mechanism / observational

Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications.

Thymosin beta 4 interactions.

Thymosin β4 Promotes Dermal Healing.

Cardioprotection by Thymosin Beta 4.

Involvement of thymosin beta 4 and endoproteinase Asp-N in the biosynthesis of the tetrapeptide AcSerAspLysPro a regulator of the hematopoietic system.

Thymosin beta 4 (T beta 4) in activated platelets.

Thymosin beta 4 and the eye: the journey from bench to bedside.

Thymosin Beta-4 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction.

Thymosin Beta-4 Induces Mouse Hair Growth.

0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial.

Actin-sequestering protein, thymosin-beta-4 (TB4), inhibits caspase-3 activation in paclitaxel-induced tumor cell death.

Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial.

Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain.