Here’s an important story that starts with a precisely targeted project that doesn’t involve aging, but then carries massive implications for longevity. You can get the full details here.
It all has to do with the thymus, a small organ located just behind the sternum. The article notes, “The thymus acts as the central hub for the development and maturation of T cells, which are instrumental in combating infections, diseases, and responding effectively to vaccinations.”
But as we get older, the functionality of the thymus declines, reducing the production of new T cells and leaving the body more vulnerable. It didn’t matter that the thymus petered out because even the reduced amount of T cells was enough when people only lived into their 40s, which was true for centuries. But now it’s a different story: “It is thought that restoring the function of the thymus has the potential to combat age-associated immune decline and a range of immune system disorders.”
Enter Dr. Stan Wang, founder and CEO of Thymmune Therapeutics, “which is developing thymic cell therapies to restore immune function in aging and disease. Backed by renowned Harvard geneticist George Church, the [company] is on a mission to use stem cells to build an ‘off-the-shelf’ thymus that could one day be offered to everyone.” In effect, this could amount to “rebooting” the immune system.
The article interviews Dr. Wang about the concept and the process.
Here’s how he sums up the issue: “The thymus is at its most active throughout the early years of life, but by the time we’re in our 20s, its function has already depleted to a minimal level. From a biological point of view, that seems to be okay for the first several decades of life. Your body cranked up a lot of naive T cells in those first two decades, and those serve to give you protection for decades. Now, as we hit our 50s, 60s, 70s and beyond, we’re seeing all these immune problems of aging. Understandably, at that point, the T cells that your body generated early in life are starting to decline as well. They’re starting to go through immunosenescence and not be able to function as well, which means they’re not as well-equipped to respond to all the threats that you encounter in life.”
Solution? In effect, a new thymus. “Biologically speaking, we think it’s relatively straightforward – we want to give everybody a new thymus gland, using an off-the-shelf cell therapy, and help everyone around the world reboot their immune system as they age. Ultimately, we believe this would help people respond better to all forms of infections, cancers, vaccines and so on, and bolster immune health on a global scale.”
OK, but how is it done?
The technique will involve “the mass production of thymic cells, derived from induced pluripotent stem cells (iPSCs).” iPSCs are a type of stem cells that has the ability to differentiate into all of the cells of the adult body (for example, heart or pancreas or liver or, in this case, thymus).
From the article: “The cells that Thymmune creates are suspended in a liquid formulation designed to be directly injected into the muscle of a subject (currently in humanised animal models, but hopefully soon in humans).” According to Dr. Wang, they “form thymic-like cells at the site of implant and injection, producing new naive T cells that can go on and mediate downstream interactions like vaccine responses, tolerance, and so on.”
Here’s where the narrower focus come in. Although the long-term goal is to deal with age-related issues, “the company is initially focused on a key area of unmet need … a rare genetic condition where children are born without a thymus.” The condition is usually fatal by age two or three.
There is already an FDA-approved method for implanting donated, surgically-harvested thymus tissue into the thigh muscle, but it’s very invasive and there’s a long waiting list. Thanks to $37 million in government funding, Thymmune is in a position to demonstrate the effectiveness and safety of its technique. “If Thymmune can demonstrate its technology is, first and foremost, safe to use in humans and then goes on to restore immune function in children born without a thymus, the company aims to continue its mission to ultimately give everyone a new thymus as they age.”
Dr. Wang sums it up: “Of course, there’s an incredible opportunity in immunology between those two extremes. There are a whole host of reasons why people end up with thymic damage or dysfunction – chemotherapy, radiation, surgery, bone marrow transplantation, and much more. Our strategy will be to start from the most clinically severe and work our way down, while ensuring we have the safest product possible, until we get to a point where we can consider this as a preventative treatment for every single one of us.”