For countless individuals, the loss of a tooth—whether due to injury, decay, or a congenital condition—marks a profound change, often affecting confidence, speech, and the simple joy of eating. Imagine a future where a single injection could awaken the body’s dormant potential to grow a new, natural tooth, rendering dentures and implants obsolete. This vision is no longer a distant dream but a tangible possibility, as Japanese scientists have embarked on a groundbreaking journey to regrow human teeth. At Kyoto University Hospital, a pioneering clinical trial is underway, testing a novel drug that could transform dental care and offer hope to millions worldwide.
The drug, known as TRG-035, represents a remarkable leap in regenerative medicine. Developed by a team led by Dr. Katsu Takahashi, a distinguished molecular biologist and dentist at Kitano Hospital in Osaka, the treatment targets a protein called USAG-1, which acts as a natural barrier to tooth development. By inhibiting this protein, TRG-035 activates dormant tooth buds—tiny, undeveloped structures present in the gums that, in most humans, never progress beyond early stages. These buds, often referred to as the remnants of a potential third set of teeth, hold the key to this revolutionary approach. In animal studies, the results were nothing short of astonishing: mice and ferrets treated with the drug grew new, fully functional teeth, indistinguishable from their natural counterparts. These teeth emerged in the correct locations, aligned with existing dental structures, and performed as well as any original tooth.
The human trials, which began in October 2024 at Kyoto University Hospital, mark the first phase of this ambitious project. The initial cohort consists of 30 adults, aged 30 to 64, each missing at least one tooth. This phase focuses squarely on safety, assessing whether the drug can be administered without adverse effects. Participants receive TRG-035 via intravenous injection, a method chosen for its precision in targeting the protein’s activity. While the primary goal is to confirm the drug’s safety, researchers are hopeful that some participants may show early signs of tooth regrowth, offering a glimpse of the treatment’s potential. Dr. Takahashi, who has dedicated over two decades to this research, expressed cautious optimism, noting that even a single instance of regrowth in this phase would be a medical triumph.
The implications of this research extend far beyond replacing lost teeth in adults. The team’s ultimate vision is to address congenital tooth agenesis, a condition affecting roughly 1% of the population, where individuals are born without some or all of their permanent teeth. This hereditary disorder, which includes severe cases like oligodontia—where six or more teeth are missing—can profoundly impact a person’s quality of life, complicating eating, speech, and jaw development. Children as young as two could benefit from this treatment, potentially growing natural teeth instead of relying on cumbersome dentures or invasive implants. The next phase of trials, planned for 2025, will focus on children aged two to seven with congenital tooth agenesis, testing the drug’s efficacy in this vulnerable population.
The journey to this point has been meticulous. Since the early 2000s, Dr. Takahashi’s team has explored the genetic mechanisms behind tooth development, building on discoveries that identified USAG-1 as a critical regulator. Their 2018 experiments with ferrets, whose dental patterns closely resemble those of humans, demonstrated that inhibiting USAG-1 could trigger the growth of a seventh front tooth in animals that naturally have six. These findings, published in prestigious scientific journals, garnered global attention and spurred the formation of Toregem Biopharma, a Kyoto University-affiliated startup tasked with commercializing the drug. The company aims to bring TRG-035 to market by 2030, pending rigorous safety and efficacy evaluations.
Dental professionals worldwide are watching closely, tempering excitement with caution. The treatment’s ability to precisely control where new teeth grow remains a key challenge, though Dr. Takahashi has suggested that orthodontic adjustments could address any misalignment. Affordability and accessibility are also critical considerations, as the team strives to ensure this innovation benefits a global population. If successful, TRG-035 could redefine dental care, offering a biological alternative to artificial solutions and potentially paving the way for regenerative treatments for other tissues and organs.
As the trial progresses, the world awaits results that could reshape smiles and lives. For those who have struggled with tooth loss, the promise of growing a new tooth—naturally, painlessly, and permanently—offers a beacon of hope. By 2030, the dream of a third set of teeth may no longer be the stuff of science fiction but a reality, thanks to the relentless dedication of Japan’s scientific pioneers.
