The thymus is a small inner organ near the heart that is responsible for the maturation of T cells of the adaptive immune system. The supply of new T cells is critical to the maintenance of effective immune function over time. Unfortunately the thymus atrophies over the course of adult life, and in most people is largely made up of inactive fat tissue by as early as 50 years of age. The resulting diminished supply of replacement cells ensures that the T cell population thereafter becomes ever more made up of malfunctioning, exhausted, and senescent cells incapable of mounting an effective response.
Given the pressing need for ways to restore lost immune function in older individuals, it is good to see that a fair number of biotech startup companies are now competing to develop means of regenerating the aged thymus. After something of an abandonment of efforts following 2010s work on FOXN1 as a regulator of thymic growth, the past few years have seen a number of programs make the leap from academia to industry. Hopefully one or more will result in a form of therapy that is both effective and cost-effective.
The primary challenge presented by the thymus is targeted delivery of therapeutics. Quite a few approaches are known to kickstart the thymus into regrowth of the active regions of tissue capable of nurturing new T cells. Unfortunately they all produce serious side-effects in other tissues when delivered at sufficient high systemic doses to ensure that enough of the therapeutic make it to the thymus. For example, delivery of recombinant keratinocyte growth factor (KGF) reliably regrows the thymus in aged mice and non-human primates. There is a human drug based on KGF, used sparingly for some complications of cancer therapy. Dosing with this drug at levels sufficient to regrow the human thymus would result in very unpleasant complications, sufficiently serious to disqualify its use in this context.
There are as yet no robustly demonstrated ways to target therapies to the thymus other than direct injection, a procedure that carries sufficient cost and risk to make it infeasible for widespread use in older individuals. Thus while the new biotech startup noted in today's article is working on a growth factor approach for thymic regeneration, in reality that means that they are working on some combination of delivery system and therapy that can limit the effects of growth factors to the target thymic tissue. That is the core challenge, delivery.
Thymus regeneration startup emerges to 'restore immune function'
Swiss biotech TECregen emerged today with seed financing to develop a pipeline of therapies designed to regenerate the thymus and boost the aging immune system. The company is built around the idea that restoring the thymus can restore immune function at its source. The gradual loss of thymic function is increasingly viewed as a biological bottleneck for healthy aging. A shrinking thymus contributes to weaker responses to vaccines, slower recovery from infections and diminished immune surveillance against emerging cancers.
TECregen is developing a class of biologic drugs it calls thymopoietics, engineered to regenerate thymic epithelial cells and rebuild the microenvironment required for effective T-cell production. Thymic epithelial cells are the structural and functional backbone of the thymus; without them, T cells cannot mature properly. By rejuvenating this cellular niche, TECregen aims to restart the production of healthy, diverse T cells and restore immune resilience across a range of conditions, from immune aging to cancer-related immune suppression.
The basis of TECregen's approach involves applying advanced ligand engineering to growth factor biology. Growth factors are potent signaling molecules that influence inflammation, tissue repair, and regeneration, including processes within the thymus. According to the company, historic attempts to use growth factors therapeutically have been hampered by systemic toxicity and poor tissue selectivity, as these molecules can trigger unwanted effects in multiple organs. TECregen aims to engineer these signals to be functionally selective and tissue-targeted, with the goal of concentrating their activity in the thymus while minimizing off-target effects.
View the full article at FightAging
