Human Trial in Japan: Tooth Regrowth Drug Advances

Every time a child loses a baby tooth and a permanent tooth grows in its place, it seems natural to us. But when an adult loses a permanent tooth, the need for an implant has always been a "sentence." The biological reason for this difference is not that we lack the infrastructure—we have it. Deep in the jaw, beneath the permanent teeth, most humans carry dormant genes for "third teeth" that have never been activated. Until now.

The Japanese company Toregem Biopharma, a spin-off of Kyoto University Hospital, launched in October 2024 the world's first clinical trial in humans of a drug aimed at activating these genes and causing a new tooth to grow biologically. As of now, the trial is already completing the initial safety phase, and safety data collection was completed in early 2026 (a final report is expected around mid-2026).

The Story of USAG-1

The team led by Dr. Katsuo Takahashi researched for about two decades why genes for additional teeth remain dormant. They identified a protein called USAG-1 (Uterine Sensitization-Associated Gene-1) that functions as a "cancel switch"—it blocks the signals (BMP) that allow third tooth genes to express.

The rationale is clear: if we block the inhibitor, the natural tooth growth signals can work again. Blocking USAG-1 increases BMP signals and enables tooth growth.

Animal Trials: Results That Led to the Clinic

In preclinical studies published in recent years, the team showed that:

• In mice engineered without certain teeth: a single dose of anti-USAG-1 antibody caused new teeth to grow within about three months in the animal model.
• In ferrets: animals that, like humans, replace teeth once, and they also grew additional normal teeth after blocking USAG-1.
• In beagle dogs with congenital tooth deficiency: the treatment also succeeded in them, and new teeth grew in the correct places, with root, enamel, and dental pulp.

In the preclinical phase, the antibody was also tested systemically (including intravenous injection) in animals. In the human trial, however, the drug is administered locally, by injection into the jaw/gum area near the missing tooth—not as a systemic infusion.

The Clinical Trial: Phase 1

The trial launched in October 2024 includes:

• 30 participants: healthy men aged 30 to 64.
• Each participant is missing at least one tooth (molar). The leading therapeutic target is severe congenital tooth deficiency (oligodontia); tooth loss from decay or trauma is a future indication and not the goal of the current trial.
• Local administration of the antibody by injection into the jaw area.
• Follow-up period with CT scans and periodic dental examinations.

The main goal at this stage is safety—to ensure there are no dangerous side effects. No participant has yet grown a tooth at this stage: this is a safety trial, not an efficacy trial. Initial safety data was collected until approximately mid-2026. Actual efficacy testing and work in children (next phase) are planned from 2027 onward.

If This Works...

The potential implications are enormous:

• End of the implant era? If a single procedure can restore a biological tooth instead of a titanium screw, there is no reason to continue with implants. A living biological tooth lasts a lifetime, connects to the nerve, and senses pressure.
• Solution for congenital tooth deficiency: About 1% of the population is born missing one or more teeth, but the leading target of the drug is specifically severe cases of oligodontia (missing six or more teeth, about 0.1% of the population). They would be the first to benefit.
• Potentially low cost: After standardization, the antibody may be cheaper than a quality implant.
• Growth time: A tooth in children develops over about 6-12 months. It is likely that here too the process will be gradual—not an immediate result.

Risks and Open Questions

Even the researchers are cautious. Several legitimate concerns:

• Unwanted teeth: If the mechanism acts excessively, a patient could develop additional teeth in incorrect places. The question is how to "direct" the growth.
• Systemic effects: USAG-1 is also active in the kidney, blood vessels, and other organs. Broadly blocking it could cause side effects in these systems—one reason they chose local administration in humans.
• Older ages: It is not yet clear if very elderly patients will retain enough local stem cells in the jaw to support growth.
• Tooth quality: Even in mice, the growing teeth were not always perfect in size and shape.

Why Japan?

Three main reasons:

• Japanese lead in stem cell research—since Shinya Yamanaka won the Nobel Prize in 2012, Japan has invested heavily in the field.
• Faster regulatory approval—Japanese PMDA laws tend to approve regenerative treatments faster than the US FDA. The drug has even received "orphan drug" status for severe congenital tooth deficiency.
• Aging population—Japan is the country with the highest percentage of elderly people in the world, creating demand for innovative regenerative treatments.

What This Means for You

If you have lost a tooth or expect to lose one in the near future—do not stop your standard treatment for this trial. Even in the best case, the drug will be commercially available only by 2030 at the earliest, and years later outside Japan. And in any case, as of now, this is a safety trial that has not yet proven tooth growth in humans. A quality implant performed today is still the best solution.

But if you are very young and have decades ahead, or if you know you will lose teeth in the future (congenital tooth deficiency, for example)—it is worth starting to follow the news from Toregem. We may be less than a decade away from an era where dentistry will be biological, not mechanical.

References:
Toregem Biopharma
The Economic Times - Tooth Regeneration Article