LIFE EXTENSION MAGAZINE

The thymus gland begins to shrivel after puberty

How Many Needless Deaths?

The thymus gland begins to shrivel after puberty, causing levels of immune peptides like thymosin alpha 1 to plummet. Studies reveal robust therapeutic potential when THYMUS GLAND thymosin is combined with conventional treatments for certain cancers, sepsis, viral infections, and autoimmune disorders. Despite thymosin alpha 1 being available 44 years ago, most Americans lack access to it.

By William Faloon.

William Faloon
William Faloon

With age, our thymus gland shrivels to the point that it no longer produces the same amount of the thymic hormones it did in youth.

Thymic hormones are important to regulate immune function.1

This decline in thymic hormones contributes to immune senescence, whereby our ability to fight infections and cancers is severely diminished, while our bodies are ravaged by chronic inflammation.1,2

In 1981, we dedicated an issue of our publication (Anti-Aging News) to the disease-fighting properties of thymosin alpha 1, an immune peptide secreted by young thymus glands.

We described how thymosin alpha 1 might soon be approved as an adjuvant cancer therapy and how it could transition into a method to reverse the decline in immune function that occurs with normal aging.

Here we are 44 years later, and despite favorable published studies and approvals in other countries,3 Americans are denied access to thymosin alpha 1.

And unlike medications that come in pill form, that Americans obtain from other countries, thymic hormones are delicate peptides that must be injected and kept cool to maintain their potency.4

In recent years, new studies revealed robust therapeutic potential when thymosin alpha 1 is combined with conventional treatments for certain cancers, sepsis, viral infections, and autoimmune disorders.5

By modulating healthy immune functions, thymosin alpha 1 boosts defenses against pathogens and malignancies while suppressing/dampening autoimmune reactions.6

This suggests that thymosin alpha 1 could potentially boost efficacy and reduce the side effects of CAR T and checkpoint inhibitor drugs that can cause inflammatory reactions in cancer patients.

With increasing evidence of safety + efficacy, thymosin alpha 1 may eventually become part of standard medical practice. We may then learn how many Americans perished because of delayed access to this natural-to-the-human-body thymic peptide.

The media redundantly touts new drugs that "harness the body’s immune system" to kill cancer cells.

Much of this media attention began in the 1980s with drugs such as interleukin-2 that have potent immune-boosting effects.7

While immune drugs shrink certain tumors and can improve tumor markers, many have not completely fulfilled their early promise.

In 2011, the first checkpoint inhibitor, Yervoy® (Ipilimumab), was introduced that makes cancer cells more vulnerable to chemotherapy, radiation, and immune attack.8

Keytruda® soon followed, that benefited those few patients who achieved durable responses, but for most, bought only a few extra agonizing months of life.9

Checkpoint inhibitors are a class of drugs that block proteins used by certain kinds of cancer cells to avoid being attacked by the immune system.10

Thymosin Alpha 1 May Improve Safety-Efficacy

Starting at puberty the thymus gland begins to atrophy and output of immune regulatory peptides (like the thymosin alpha 1) plummets.

By the time cancer incidence spikes in Americans (average age 66 years),11 there are severe declines of immune functions.12

While drug classes like interferons, certain interleukins, and checkpoint inhibitors have favorable immune properties, there is evidence they might work better in combination with thymosin alpha 1.

An abundance of published data reveals that combining standard therapies with thymosin alpha 1 can significantly improve treatment efficacy and reduce toxicities.4,13-16

One retrospective study showed median overall survival in advanced-stage melanoma patients was 58 months when thymosin alpha 1 was administered before the checkpoint inhibitor drug Yervoy®. When Yervoy® was administered alone to advanced-stage patients, median overall survival was only seven months.17

This study provided stark data demonstrating the potential benefits of bolstering immune functions with thymosin first, and then following with a checkpoint inhibitor to remove tumor cell barriers that preclude immune destruction.

An overview analysis published in 2019 titled "A Reappraisal of Thymosin Alpha 1 in Cancer Therapy" used the term "combination" 38 times to describe how adding thymosin alpha 1 could improve clinical outcomes when combined with other therapies.18

These data likely motivated the FDA to consider approving thymosin alpha 1 for stage 4 (advanced) melanoma patients, but we don’t see FDA follow through for compassionate use.19-22

My question is: why not let early-stage melanoma and other cancer patients try thymosin alpha 1 when there may be a better opportunity to induce a complete response?

Discovery of Thymosins in 1966

The extraction of thymosins dates back to the year 1966 (59 years ago)!23

By 1966-1968, published research showed that thymosin was able to restore immune functions in mice whose thymus glands were surgically removed.24

In 1977, a published review of clinical studies described the immune-potentiating effects of thymosin alpha 1 in immune-deficient cancer patients.25

Early studies starting in 1978 were already showing benefits with thymosin alpha 1 in cancer patients undergoing conventional therapies.26,27

The November 1981 issue of our publication (Anti-Aging News) advocated for widespread study and clinical application of thymosin alpha 1 to combat tumors and prevent opportunistic infections caused by the immune-suppressive effects of surgery, chemo, and radiation therapies.

"The FDA’s restriction appears unfounded, as thymosin a1 has shown safety and efficacy beyond the initially specified conditions."38

Decades of Research

Published studies elucidate in greater detail the many immune-modulating mechanisms of thymosin alpha 1,5,6,14,28,29 a hormone that abundantly circulates in younger people, but virtually disappears with older age and the onset of immune senescence.

A number of clinical trials found that thymosin alpha 1 increased survival and reduced progression of metastatic disease in patients with advanced cancer, when used with standard cancer treatment.16,17,30,31

Thymosin has multiple mechanisms that may account for the observed benefits, including preventing the tumor-induced reduction of natural killer (NK) cell activity and preserving the barrier integrity that keeps tumor cells from spreading.18

Additional lab data show that:

• When combined with alpha-beta interferon, administration of thymosin alpha 1 can stimulate NK activity in chemotherapy-immune- suppressed mice.32

• Mice inoculated with melanoma or lung cancer cells had restored NK cell activity if treated with thymosin alpha 1 and alpha-beta interferon 10 days after tumor inoculation.33,34

• The anti-tumor effects were improved in melanoma-bearing mice by the combined chemo-immunotherapy using high doses of thymosin alpha 1 and low dose alpha-beta interferons in combination with the chemo-therapeutic drug cyclophosphamide.35

In an animal model study, the combination of thymosin alpha 1 and alpha-beta interferon restored the function of NK cells in animals with suppressed NK function after chemotherapy treatment. This demonstrates the potential value of combination immune treatments, including for fighting cancer.32

We’ve long advocated that thymosin alpha 1 be considered in early-stage cancers when there is a realistic opportunity for a durable complete response as opposed to mere improved survival.

Recent published reviews of scientific literature (2018-2024) increasingly recognize thymosin alpha 1 as a potential adjuvant therapy for sepsis, viral infections, and malignancies beyond lung cancer, hepatocellular carcinoma, and melanoma.4,18,36-38

Why Thymosin Was Not Approved in the United States

In the period of 1984-1988, a company called Alpha 1 Biomedical conducted a clinical trial testing thymosin alpha 1 in lung cancer patients.

While some patients benefited, the clinical trial did not yield sufficient statistical data to meet the FDA’s stringent criteria. I was told that if just ONE more patient in this trial achieved predefined clinical endpoints that thymosin alpha 1 would have been approved as a cancer drug.

But let’s make it very clear: thymosin alpha 1 by itself is not a miraculous cancer cure.

It offers cancer patients an immune boost to make existing therapies more effective and less toxic. This may be of particular value to cancer patients using checkpoint inhibitor drugs (Keytruda®, Optivo®, Yervoy®, CAR T, others.)

There should be more study on combining thymosin with other immune modulators such as differing interferons, interleukin-2 and/or granulocyte colony stimulating factor (G-CSF). Since these drugs are off-patent, there is little economic incentive to initiate clinical trials that cost tens of millions of dollars.

And as we advocated 44 years ago, thymosin alpha 1 should be studied in humans over age 65 who almost all suffer dangerous declines in immune function, i.e., immune senescence.

This month’s issue reprints the article and editorial we published back in November 1981. We do this to capture the attention of those who wonder why 612,000 Americans will perish from cancer this year and another 350,000 from sepsis…with scant improvements in survival curves.

We at Life Extension continue to opine that many of these lives could be spared if thymosin alpha 1 were approved as an affordable generic drug in the United States.

For longer life,

For Longer Life

William Faloon, Co-Founder, Life Extension®

References

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