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Activation of Telomerase by TA-65 Enhances Immunity and Reduces Inflammation Post Myocardial Infarction

Bilal Bawamia, Luke Spray, Vincent K Wangsaputra, Karim Bennaceur, Sharareh Vahabi, Konstantinos Stellos, Ehsan Kharatikoopaei, Emmanuel Ogundimu, Chris P Gale, Bernard Keavney, Rebecca Maier, Helen Hancock, Gavin Richardson, David Austin, Ioakim Spyridopoulos

GeroScience (2023)

Background

Myocardial infarction (MI), or heart attack, is a major medical condition that increases the risk of recurrent cardiovascular events or death. One contributing factor to these adverse outcomes is the premature aging of the immune system, also known as "immunosenescence." Recent research focuses on the effects of TA-65®, an oral telomerase activator, and its potential for counteracting immune cell aging in post-MI patients. Prior studies and pre-clinical data indicate that TA-65® may reduce immune system aging and inflammation after an MI.

Study Model

The TACTIC trial was a single-center, randomized, double-blind, parallel-group, placebo-controlled phase IIa pilot study, involving 90 participants diagnosed with coronary heart disease and MI within the previous 6 months. Participants received either 8 mg doses of TA-65® or a placebo, twice daily for 12 months. The trial focused on patients aged 65 and over, with acute MI within the last six months, who had undergone successful revascularization or were under medical management following MI. Those with conditions causing immunological dysfunction, clinical instability, severe uncontrolled hypertension, severe comorbidities likely to affect the outcome over the next two years, or other specific conditions were excluded.

The trial employed multiple assays to track the response to TA-65® treatment, including flow cytometric analysis of leucocytes, quantifying nuclear telomerase activity in peripheral blood mononuclear cells (PBMCs) using the Telomerase Repeated Activation Protocol (TRAP) – quantitative polymerase chain reaction (qPCR) assay, and evaluating oxidative stress using the TBARS colorimetric assay.

Findings, Method of Action

The trial findings revealed that TA-65 treatment resulted in a significant increase in the mean total lymphocyte count after 12 months. This elevation was primarily due to a significant increase in CD3+, CD4+, and CD8+ T-lymphocytes, B-lymphocytes, and natural killer cells from baseline. No such increase was observed in the placebo group. Additionally, the TA-65® group saw a 62% reduction in hsCRP, an inflammation marker, compared to the placebo group after 12 months. Importantly, the TA-65® group also experienced significantly fewer complications, such as chest or joint pains, after their heart attack.

Looking at the mechanism of action, mitochondrial telomerase activation emerges as a potential pathway through which TA-65® exerts its effects. Telomerase activation within mitochondria could improve their function, contributing to overall cellular health and vitality. This could particularly aid in rejuvenating T cells, which often undergo mitochondrial dysfunction leading to senescence and Inflammaging - a state of chronic inflammation associated with aging.

Findings, Health Effects

The TACTIC trial findings suggest that TA-65® could enhance immune cell health and reduce inflammation, potentially delaying the progression of coronary atherosclerosis and reducing heart failure incidence in post-MI patients. The trial showed that TA-65® not only reduces inflammation but also appears to boost immunity by increasing patients' immune cells.

Findings, Safety

TA-65® demonstrated a favorable safety profile, with significantly fewer adverse events observed in the TA-65® group compared to the placebo group. Few adverse effects, such as fever or new medical problems, occurred following the heart attack in the TA-65® group, which showed 30% fewer adverse effects than the group given the placebo. This positive safety profile, in conjunction with the observed health benefits, suggests that TA-65® could serve as a promising new therapeutic approach for post-MI patients.

Conclusion

The findings from the TACTIC trial underline the potential of TA-65® in combating immunosenescence and enhancing immune function, especially in post-MI individuals. TA-65® distinguishes itself with its ability to significantly curb inflammation, reducing it by up to 62%, while simultaneously enhancing immunity by increasing the count of immune cells. This dual action is truly noteworthy considering that many potent anti-inflammatory drugs tend to suppress the immune system. Moreover, its favorable safety profile makes TA-65® a compelling therapeutic option in managing the common residual concern of immunosenescence after MI.

Explore the Complete Study

Delve into the comprehensive details of our groundbreaking research by accessing the full study at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122201/

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