Japanese drug reactivates tooth buds
- Kitano Hospital in Osaka said it began a first-in-human trial of TRG035, a humanized anti-USAG-1 antibody, after Japan’s PMDA cleared the study on March 25, 2024. - The study is a phase 1 single-dose, randomized, placebo-controlled trial at Kyoto University Hospital, scheduled from September 2024 to August 2025 in men ages 30 to 64. - The drug targets congenital oligodontia, a condition affecting about 0.1% of people with six or more missing teeth, after mouse and beagle studies restored tooth formation. (kitano-hp.or.jp)
Teeth form from tiny early structures called tooth buds, like seeds that usually either grow on schedule or stay silent. Japanese researchers are testing whether blocking a protein called USAG-1 can let some of those buds keep developing. (kitano-hp.or.jp) (pubmed.ncbi.nlm.nih.gov) The specific drug is TRG035, a humanized antibody designed to neutralize USAG-1 rather than edit DNA. Kitano Hospital in Osaka said on May 3, 2024 that it had started an investigator-initiated clinical trial after Japan’s Pharmaceuticals and Medical Devices Agency approved the plan on March 25, 2024. (kitano-hp.or.jp) The first study is a phase 1, single-dose, double-blind, randomized, placebo-controlled dose-escalation trial. It is being run with Kyoto University Hospital’s early clinical development unit and was scheduled for September 2024 through August 2025. (kitano-hp.or.jp) This first phase is about safety, not proving new teeth will grow in patients. Kitano Hospital said the initial volunteers are healthy adult men ages 30 to 64 who are missing at least one molar, and that the study is not recruiting patients with the congenital disorder yet. (kitano-hp.or.jp) The disorder the team ultimately wants to treat is congenital oligodontia, where a person is born missing six or more permanent teeth. Kitano Hospital puts its frequency at 0.1%, and says current care is largely limited to dentures or implants after adulthood. (kitano-hp.or.jp) The science behind the drug comes from years of animal work on USAG-1, a protein that suppresses signals involved in tooth development. A 2021 Science Advances paper reported that anti-USAG-1 antibody treatment restored tooth formation in mouse models of congenital tooth agenesis. (science.org) (kyoto-u.ac.jp) Kitano Hospital said later preclinical work also restored missing teeth in model mice and beagle dogs, and that those results led the team to choose TRG035 as its final development candidate. A 2024 review in The Japanese Dental Science Review said the phase 1 framework had been finalized and preparations were underway. (kitano-hp.or.jp) (pubmed.ncbi.nlm.nih.gov) The company commercializing the work, Toregem BioPharma, says the next planned step after phase 1 is a phase 2a study in congenital oligodontia patients. Kitano Hospital said that later study is aimed at children ages 2 to 7 with four or more congenitally missing teeth. (toregem.co.jp) (kitano-hp.or.jp) Japan’s health ministry gave TRG035 orphan-drug designation in September 2025 for severe congenital oligodontia, according to Toregem. The company also said in November 2025 that it had received a response from a pre-Investigational New Drug meeting with the United States Food and Drug Administration. (toregem.co.jp) For now, the story is not that dentists can regrow teeth on demand. The verified update is narrower: a Japanese team moved an anti-USAG-1 tooth-regeneration drug from mice and dogs into an early human safety trial, with congenital missing teeth as the first target. (kitano-hp.or.jp) (pubmed.ncbi.nlm.nih.gov)
