TB-500 : données probantes, mécanisme et limites

Thymosin beta-4 is a naturally occurring repair molecule that platelets release at sites of injury. TB-500 is a short fragment of it. FDA's list of bulk drug substances that may present significant safety risks identifies TB-500 as the thymosin beta-4 fragment with the sequence LKKTETQ.

Pharmaceutical research has studied full-length thymosin beta-4 instead of the fragment. Safety and efficacy data from those programs do not automatically transfer to TB-500.

A review of full-length thymosin beta-4 in skin repair describes it as promoting cell migration and the mobilization and differentiation of stem cells, while limiting inflammation, cell death and infection. The same review reports faster healing of skin wounds in rats and mice.

These actions were described for the full-length molecule. They are largely extrapolated to the consumer fragment without direct evidence.

No controlled human trial of TB-500 has been published, and FDA states that it has not identified any human exposure data for drug products containing the fragment.

Human studies of full-length thymosin beta-4 have focused on eye and skin wound uses. A small phase 2 randomized trial of thymosin beta-4 eye drops in nine people with severe dry eye reported improved signs and symptoms compared with vehicle. Two phase 2 trials in pressure and stasis ulcers reported faster healing in the patients who healed. A phase 1 randomized study in healthy volunteers found intravenous recombinant thymosin beta-4 well tolerated, as groundwork for trials in heart attack; three of its authors were employees of the sponsor.

None of these trials tested tendon, muscle, ligament or joint repair, which are the uses most often claimed for TB-500. Full-length thymosin beta-4 is not approved for any indication.

Safety in people is unknown for TB-500. FDA says compounded drugs containing the fragment may carry a risk of immune reactions (immunogenicity) for some routes because the peptide can aggregate, and may contain peptide-related impurities. FDA lacks information on whether it would cause harm in humans.

A theoretical concern follows from the pro-migratory, pro-repair mechanism: such activity could in principle support unwanted tissue or tumor growth. No long-term safety data exist for the fragment.

TB-500 is not approved by the FDA or Health Canada for any indication. WADA lists thymosin beta-4 and its derivatives, naming TB-500 as an example, under S2 (peptide hormones, growth factors, related substances and mimetics), which are prohibited at all times. The NCAA banned substances list also names TB-500.