Japan Plans First Child Trial Of A Tooth-Regrowth Drug. Proof It Works In People Is Still Missing

Most people get two sets of teeth, and after that, a lost tooth is gone for good. Dentures, bridges and implants can fill the gap, but none of them is a tooth that grew back. So when headlines began describing a Japanese drug that could coax out a “third set,” the idea spread quickly.

The research behind it is narrower, and for some families more important. The antibody, called TRG035, has grown teeth in mice and ferrets, and its developer says it passed a safety trial in healthy men. Its first planned patients are children born missing many permanent teeth. Whether it can grow a working tooth in any person is still unknown, and so is the claim at the heart of those headlines: that everyone carries a spare set waiting to come in.

Is There Really A Complete Third Set Waiting?

No. In a 2023 review in Regenerative Therapy, researchers from Kitano Hospital in Osaka and Kyoto University use “third dentition” for tooth-forming potential beyond baby teeth and adult teeth. Part of their evidence comes from people who grow extra teeth, which the same research group traced in CT scans to this third line of development. That points to occasional extra teeth in some people, not a full row of buds in every adult jaw.

The drug targets a protein called USAG-1, also known as SOSTDC1, which works like a brake on tooth development. It dampens two chemical signaling systems, BMP and Wnt, that help decide whether a young tooth bud keeps growing or stops. Blocking USAG-1 might let a stalled tooth bud start developing again, an approach that fits congenital tooth agenesis, a condition in which some teeth never form.

Why Did Researchers Think This Could Work?

Because of animal experiments under carefully chosen conditions. In a 2021 study in Science Advances, the Kyoto-led team worked with mice bred with gene defects that leave them missing teeth. Shutting off USAG-1, either by deleting its gene or by injecting antibodies against it, brought back some of the missing teeth. In normal mice, a single dose of one antibody produced extra teeth.

Not every antibody was safe for the animals. Of the five the team tested, three led to low birth and survival rates in mice. The researchers concluded that blocking USAG-1’s effect on BMP mattered more for tooth growth than blocking its effect on Wnt, though they wrote that a role for Wnt could not be ruled out. BMP and Wnt signaling work throughout the body, not just in teeth, so unintended effects on development remain a central safety question.

The team also tested ferrets, which, like humans, grow baby teeth and then permanent ones. Ferrets dosed in their first weeks of life grew an extra front tooth that the authors said might count as third dentition. Getting that tooth took a five-times-higher concentration of antibody, three injections and drugs to suppress the immune system. The work did not show that an adult could replace a lost tooth.

What Have Human Trials Actually Shown?

Safety so far, according to the developer. Japan’s clinical trial registry lists the first human study, run at Kyoto University Hospital, as a randomized, double-blind, placebo-controlled trial. It tested single intravenous doses in 30 healthy men ages 30 to 64, each missing at least one molar. Its listed outcomes are safety, how the drug moves through the body and whether volunteers made antibodies against it. Tooth growth is not one of them.

In a November 27, 2025 announcement about a meeting with the U.S. Food and Drug Administration, Toregem said it had finished the Phase I trial, “confirming its safety.” The registry entry shows no adverse-event counts or dose-by-dose results, and the detailed results have not been made public for independent review.

The next study moves into patients. On August 17, 2026, Toregem announced that Japan’s drug regulator, the Pharmaceuticals and Medical Devices Agency, had finished reviewing its notice for a Phase IIa trial. Hospital review boards still have to sign off before children can be enrolled and dosed. According to Dentistry, the study will test doses in 24 children with severe congenital tooth agenesis. It is open-label, meaning everyone knows who gets the drug, and it has no comparison group. Toregem’s orphan-drug announcement defines the severe form as missing six or more permanent teeth from birth. Clearing that regulatory review is not the same as approval.

What Does The 2030 Goal Actually Mean?

It’s a development target, with major questions still open. Kitano Hospital’s patient information site plans Phase IIa and IIb trials from 2026 to 2028, a larger Phase III trial from 2027 to 2029 and a Japanese approval application in 2029, with 2030 as the year it hopes to bring a prescription drug to market. The hospital also lists a follow-up project to develop MRI imaging markers and run observational studies after the Phase I trial.

That schedule assumes the Phase II trials show the drug helps children without unacceptable harm. The program has moved past a laboratory idea. The real test is whether it can safely grow a tooth that comes in at the right spot, forms a solid root, anchors in the jawbone and works in a child’s bite. In ferrets, the extra tooth appeared to be growing a shorter root than normal, a reminder of how much still has to be shown in people.

This article is for general information only and is not medical advice. Families concerned about missing teeth should speak with a dentist or pediatric dental specialist.