Japan Completes First Human Trial of Tooth-Regrowth Drug Blocking USAG-1 Protein

Researchers are investigating whether inhibiting the protein USAG‑1 could lift a natural block on tooth formation, a strategy that has already yielded promising results in mouse models.

For many years, dental restoration has relied on prosthetics such as dentures and implants. A team in Japan is now exploring a biologically driven alternative that taps into the body’s own developmental pathways. At this point, the work is still in the safety‑assessment phase rather than proving clinical effectiveness in people.

USAG‑1: A Key Regulator of Dental Morphogenesis

The investigation stems from earlier findings that manipulating USAG‑1, a protein that modulates tooth development, can change the number of teeth in rodents. A 2021 article in Scientific Reports demonstrated that local inhibition of USAG‑1 altered tooth count in mice, prompting the design of a drug that blocks the protein to encourage new tooth growth.

Katsu Takahashi, who leads the dentistry and oral surgery division at the Medical Research Institute Kitano Hospital in Osaka, has dedicated his career to unraveling the genetic factors that dictate dental number. His work focuses on the pathways that limit how many teeth develop.

“The idea of growing new teeth is every dentist’s dream. I’ve been working on this since I was a graduate student. I was confident I’d be able to make it happen,” Takahashi told Mainichi. He also said, “We’re hoping to see a time when tooth regrowth medicine is a third choice alongside dentures and implants.”

Takahashi notes that “the number of teeth varied through the mutation of just one gene,” suggesting that a single molecular target could shift dental patterning in humans.

First‑In‑Human Safety Study Completed

The program has moved from animal work to a Phase I clinical trial in Japan, listed on the national trials portal as the inaugural human assessment of the candidate drug TRG035.

The study enrolled 30 healthy men aged 30 to 65 who were missing at least one molar. Participants received a single dose of the investigational agent across five escalating concentrations (0.4 mg/kg to 24.0 mg/kg). The primary goal was to confirm safety rather than to prove tooth regrowth.

Toregem BioPharma, the company developing TRG035, announced the completion of the domestic Phase I trial. While the safety data are now available, the trial does not yet demonstrate that the drug can actually regenerate teeth in patients.

Scientific interest continues to grow. A 2023 paper in Regenerative Therapy highlighted anti‑USAG‑1 antibodies as a potential avenue for treating human tooth anomalies, noting the absence of any approved tooth‑regeneration therapy. A 2026 review in Stem Cell Reviews and Reports took a more measured tone, describing USAG‑1 as a developmental gatekeeper and suggesting that anti‑USAG‑1 approaches might only be viable under tightly controlled conditions.

Targeting Congenital Tooth Absence

The initial therapeutic focus is not on adults who lose teeth due to decay or trauma, but on individuals born with severe forms of tooth agenesis—specifically, those missing six or more permanent teeth, a condition affecting roughly one in a thousand people.

Toregem’s own materials emphasize that the drug aims at the “third dental crest,” a hypothetical additional dentition that could be coaxed into forming with anti‑USAG‑1 treatment. However, the company has yet to show that a regenerated tooth can emerge in the correct location, integrate with surrounding bone and gum tissue, and function without complications.

Funding for the project remains robust. In May 2026, the firm disclosed a pre‑Series C round of about ¥850 million (approximately $5.3 million), bringing total financing—including public grants—to over ¥4.6 billion ($29 million). The capital is earmarked for Phase II trials in Japan and for laying groundwork for future development in the United States.

Toregem envisions a commercial launch around 2030, but as of now, only early‑stage safety data are available, and no evidence yet confirms that the therapy can produce a functional, clinically viable tooth in humans.