Japan begins human trial of drug to regrow missing teeth

The promise of a new tooth is now sitting in a clinical trial, not a lab dish. At Kyoto University Hospital, researchers began testing TRG-035, an antibody drug built to block the USAG-1 protein and release dormant tooth buds, in a first-phase study focused on safety and dose finding.

The trial enrolled 30 healthy adult men, roughly 30 to 64 years old, who were missing at least one tooth. That first step matters because the team is not starting with routine tooth loss from decay or injury. It is aiming at congenital tooth absence, especially hypodontia, oligodontia and anodontia, conditions that can affect children early and disrupt nutrition, growth, chewing, speech, appearance and psychological well-being.

The science behind the trial grew out of work Kyoto University researchers reported in 2021, when an anti-USAG-1 antibody stimulated tooth growth in mice with congenital tooth agenesis. The normal adult mouth has 32 teeth, and about 1% of the population has more or fewer teeth because of congenital conditions. In other words, this is not about cosmetically replacing a lost crown. It is about whether a protein signal that normally helps shape development can be controlled in adults well enough to regenerate an entire missing tooth.

Katsu Takahashi has led the tooth-regeneration effort for years through Kyoto University and the Medical Research Institute Kitano Hospital in Osaka. Japan’s Agency for Medical Research and Development recorded 243.1 million yen in support for the 2022 to 2024 project, with a stated goal of developing a single intravenous dose of TRG-035 that could restore permanent teeth and the supporting alveolar bone. That detail puts the work squarely in the regenerative-medicine lane: the target is not a patch or a prosthetic, but a biological replacement that can integrate with the jaw.

Toregem BioPharma, the Kyoto University spinout founded in March 2020 to commercialize the therapy, has called TRG035 the world’s first antibody drug to neutralize USAG-1. Japan’s Ministry of Health, Labour and Welfare designated it an orphan drug on September 29, 2025, for severe congenital oligodontia. If the early human data hold up, later testing could extend to children with congenital tooth loss, and Takahashi has said the goal is to make regrowth a third option alongside dentures and implants. For now, the real milestone is narrower: proving that a developmental protein signal can be safely switched off in adults without creating new problems while it gives missing teeth a second chance.