TB-500 Dosing Protocol: Research-Based Guidelines

Finally, translational opportunities are appraised with attention to pharmacokinetics, peptide stability and delivery strategies. Key challenges moving forward include validating efficacy in additional clinically relevant models, overcoming peptide instability and completing comprehensive safety assessments.

Limitations: No placebo control reported. Review article — no new primary data.

In summary, glutamine effectively ameliorated inflammation and the occurrence of apoptosis by downregulating the pro-inflammatory and pro-fibrotic corneal epithelial cells subclusters and the related IκBα/NF-κB signaling. The present study suggests that glutamine metabolism plays a critical, previously unrecognized role in DED and proposes an attractive strategy to enhance glutamine metabolism by inhibiting the enzyme GLS1 and thus alleviating inflammation-driven DED progression.

Limitations: No placebo control reported.

The beneficial effects of Tβ4 were also revealed in 5xfAD model mice. Thus, this study has identified Tβ4 as a neuroprotective factor that may mitigate altered neurogenesis and AD pathology, highlighting a potential for disease intervention.

Limitations: No placebo control reported.

pDC depletion during house mite dust challenge enhanced CCR2-dependent inflammatory monocyte-derived cell accumulation, leading to exacerbated TH2-mediated allergic asthma phenotypes. RNA-sequencing analysis revealed that the anti-inflammatory peptide thymosin β4 (Tβ4) was among the most upregulated genes in asthmatic lung pDCs.

Limitations: No placebo control reported.

Plasma CCN5 levels were significantly reduced and correlated closely with the degree of restenosis in ISR patients. CCN5 expression was significantly decreased in VSMCs of stent-implanted porcine coronary segments and injured mouse femoral arteries, especially in synthetic VSMCs.

Limitations: No placebo control reported.

This process mitigates oxidative stress, reduces apoptosis, and promotes revascularization, thereby improving the quality and volume retention of fat grafts. Our findings provide a novel mechanistic insight into the enhancement of fat graft survival and suggest that mitochondrial transplantation and Tβ4 are potential therapeutic strategies to improve clinical outcomes in autologous fat transfer procedures.

Limitations: No placebo control reported.

Furthermore, MN@EVsTβ4 patches showed significant efficacy in reversing senescence and promoting wound healing in diabetic wound models. Thus, the engineered ADSC-EVs, combined with separable microneedle patches, represent a promising bioengineering strategy for clinical wound management.

Limitations: No placebo control reported.

The simultaneous analytical method for TB-500 and its metabolites was developed and validated. The study found that Ac-LK was the primary metabolite with the highest concentration in rats at 0-6 h intervals.

Limitations: No placebo control reported.

Moreover, as our initial results imply, it is not the differentiated, yet most likely the local epidermal progenitor cells which are the primary targets of the molecule. Our present results unveil a new, thus far undiscovered field regarding clinical utilization for TB4 in the future.

Limitations: No placebo control reported.

Endothelial Sirt1 deficiency, by inhibiting autophagy and activating nuclear factor-kappa B signaling, augments expression and secretion of thymosin beta-4 (Tβ4) that promotes insulin signaling in skeletal myotubes. Thus, unlike in skeletal myocytes, Sirt1 deficiency in the endothelium promotes glucose homeostasis by stimulating skeletal muscle insulin sensitivity through a blood-borne mechanism, and augmented secretion of Tβ4 by Sirt1-deficient endothelial cells boosts insulin signaling in skeletal muscle cells.

Limitations: Animal study only — human translation uncertain.

Moreover, we discovered TB4 is capable of epicardial progenitor activation, and revealed the effect is independent of hypoxic injury. By observing the above results, we believe, further discoveries and consequential postnatal administration of developmentally relevant candidate molecules such as TB4 may likely result in reversing aging processes and accelerate organ regeneration in the human body.

Limitations: No placebo control reported. Review article — no new primary data.

It prevented LPS-induced amyloid burden in APP/PS1 mice but increased astrocytic and microglial proliferation in the hippocampus of LPS-treated WT mice. These data show that Tβ4 can alleviate the adverse effects of systemic LPS in the brain by preventing exacerbation of amyloid deposition in AD mice and by inducing reactive microgliosis in aging WT mice.

Limitations: Animal study only — human translation uncertain.

Adjunctive thymosin beta 4 treatment holds novel therapeutic potential to regulate and, optimally, resolve disease pathogenesis in the cornea and perhaps other infectious and immune-based inflammatory disease. We plan to establish the importance of thymosin beta 4 as a therapeutic agent in conjunction with antibiotics with high impact for immediate clinical development.

Limitations: No placebo control reported.

Interestingly, a balance of neurotrophic factors (nerve growth factor and brain-derived neurotrophic factor) and receptors (nerve growth factor receptor p75, tropomyosin related kinase A and B) were competitively maintained by Tβ4 through receptors reacting to PrP (106-126). Our results demonstrate that Tβ4 protects neuronal cells against PrP (106-126) neurotoxicity via the interaction of neurotrophic factors/receptors.

Limitations: No placebo control reported.

We demonstrated that Tβ4 protein level elevated in all APP/PS1 mice. Over-expression of Tβ4 alone alleviated AD-like phenotypes of APP/PS1 mice, showed less brain Aβ accumulation and more Insulin-degrading enzyme (IDE), reversed phenotypic polarization of microglia and astrocyte to a healthy state, improved neuronal function and cognitive behavior performance, and accidentally displayed antidepressant-like effect.

Limitations: Animal study only — human translation uncertain.

However, no research has been done to investigate the effects of Tβ4 on NAFLD. Based on the findings above mentioned, we hypothesize that Tβ4 may represent an effective treatment for NAFLD.

Limitations: No placebo control reported. Review article — no new primary data.

These results suggest that Tβ4 may play a critical role in barrier stabilization. Furthermore, Tβ4 may prevent neurodegenerative diseases caused by prion-induced BBB dysfunction.

Limitations: No placebo control reported.

It is speculated that F-actinemia contributes to microcirculatory perturbations present in patients with sepsis by disturbing laminar flow. Given that Thymosin Beta 4 inhibits the polymerization of F-actin, it is possible that Thymosin Beta 4 decreases mortality in sepsis via the regulation of actin as well as its other anti-inflammatory properties and should be further pursued as a clinical trial in humans with sepsis.

Limitations: No placebo control reported. Review article — no new primary data.

Expert opinion: The electrifying possibility of Tβ4 as a revolutionary novel dry eye therapy is something that could have only been dreamed about just a few years ago. We believe that Tβ4 eyedrops will help many patients suffering from several ocular surface related disorders.

Limitations: No placebo control reported. Review article — no new primary data.

We further highlight three factors that may confound TB4 clinical measurements and should be considered in future study design: 1) residual platelets remaining in suspension after centrifugation, 2) TB4 release following ex vivo platelet activation, and 3) specificity of assays towards posttranslational modifications. Accordingly, we put forth our recommendations to minimize residual and activated platelets during sample collection, and to cross-validate TB4 measurements using both antibody-based and mass spectrometry-based methods.

Limitations: No placebo control reported. Review article — no new primary data.

AREAS COVERED: The authors provide an overview of the Tβ4's anti-inflammatory properties in several pathologies and provide preliminary evidence on the ability of Tβ4 to resolve inflammation via the promotion of non-canonical autophagy associated with the activation of the DAP kinase anti-inflammatory function. EXPERT OPINION: Based on its multitasking activity in various animal studies, including tissue repair and prevention of chronic inflammation, Tβ4 may represent a potential, novel treatment for inflammatory diseases associated with defective autophagy.

Limitations: Preliminary/pilot study — needs larger trials. No placebo control reported. Review article — no new primary data.

Variation in effects and effect sizes in animal models may potentially be due to variable distribution of Tβ4. Preclinical studies of PK/PD relationships and a reliable pharmacodynamic biomarker would facilitate clinical development of Tβ4.

Limitations: No placebo control reported. Review article — no new primary data.

Tβ4 also accelerated the rate of repair in phase 2 trials with patients having pressure ulcers, stasis ulcers, and epidermolysis bullosa wounds. It is safe and well tolerated and will likely have additional uses in the skin and in injured organs for tissue repair and regeneration.

Limitations: No placebo control reported. Review article — no new primary data.

Although the role of Tβ4 has not been elucidated, it is apparent that Tβ4 is associated with HSC activation. Therefore, understanding the potential roles and regulatory mechanisms of Tβ4 in liver fibrosis may provide a novel treatment for patients.

Limitations: No placebo control reported. Review article — no new primary data.

Tβ4 is expressed endogenously in the activated HSCs, but this endogenous Tβ4 displays opposite effects in HSC activation, either as an activator or an inhibitor. Although the role of Tβ4 has not been established, it is apparent that Tβ4 influences HSC activation, suggesting that Tβ4 is a potential therapeutic target for treating liver diseases.

Limitations: No placebo control reported. Review article — no new primary data.

Mechanistically, Tβ4-overexpressing mice showed increased protein expression levels and phosphorylation of P38, ERK and AKT, whereas knockout mice had decreased levels of both expression and phosphorylation of these proteins. Tβ4 appears to regulate P38/ERK/AKT signaling via its effect on VEGF expression, with a resultant effect on the speed of hair growth, the pattern of HFs and the number of hair shafts.

Limitations: No placebo control reported.

Gene expression analysis suggested a thymosin beta 4-dependent regulation of mesenchymal signature genes and modulation of TGFβ and p53 signalling networks. We conclude that thymosin beta 4 should be explored as a novel molecular target for anti-glioma therapy.

Limitations: No placebo control reported.

Some of these effects are consistent with beta-thymosins functioning exclusively as monomer-binding proteins, while others are not. Therefore, the complex pleiotropic effects of beta-thymosin in cells may be due to direct and indirect effects on the actin cytoskeleton, as well as modulation of signaling pathways that will impact the cytoskeleton and a variety of cell functions.

Limitations: No placebo control reported. Review article — no new primary data.

Treatment of cultured breast cancer cells (SK-BR-3) with 1-4 microg thymosin beta-4/mL significantly increased cell numbers, as determined by MTT-assays. These data reveal an unexpected cellular heterogeneity of thymosin beta-4 expression in breast and colonic carcinomas and suggest that local release of this polypeptide in the tumor microenvironment may modulate tumor behavior.

Limitations: No placebo control reported.

The ability of Tbeta-4 to promote coronary vessel development and potentially induce new vasculature in the adult is essential for cardiomyocyte survival and could contribute significantly toward the reported Tbeta4-induced cardioprotection and repair in the adult heart. Tbeta-4 is currently subject to multicenter phase 1 clinical trials for treatment of cardiovascular disease (http://www.regenerx.com), therefore, insight into the repair mechanism(s) induced by Tbeta-4 is an essential step toward harnessing therapeutic survival, migration, and repair properties of the peptide in the context of acute myocardial damage.

Limitations: Animal study only — human translation uncertain. Review article — no new primary data.