Somewhere in your mouth right now, there are tooth buds that never became teeth. Your body grew them, then stopped them, and has kept them dormant ever since. For nearly all of human history, that was the end of the story. Once your permanent teeth came in, that was it – two sets and done. But a team of researchers in Japan has spent the better part of three decades asking whether that biological stop signal can be reversed, and in October 2024, they moved that question from the laboratory into living human bodies.
Dr. Katsu Takahashi, head of dentistry and oral surgery at the Medical Research Institute Kitano Hospital in Osaka, has been working on this problem for nearly three decades. The turning point came when his team noticed that mice lacking a specific protein grew more teeth than normal. That observation led to the drug now being tested in people, and to a clinical trial with no prior precedent in dentistry.
Although the normal adult mouth has 32 teeth, about 1% of the population has more than this due to hyperdontia, a congenital condition. Those numbers indicate that the biological machinery for growing additional teeth exists in humans – it just gets switched off. Takahashi’s team identified what does the switching, and how to interfere with it.
The Protein That Stops Your Teeth From Growing
Scientists at Kyoto University and the University of Fukui found that an antibody targeting one gene – uterine sensitization associated gene-1, or USAG-1 – can stimulate tooth growth in mice with tooth agenesis, a congenital condition. USAG-1 acts as a biological brake, suppressing the signals that would otherwise allow dormant tooth buds to develop into full teeth.
The drug blocks USAG-1 and promotes the differentiation of underdeveloped tooth structures into fully formed teeth. In practical terms, the antibody tells the body’s existing tooth buds to restart the development process they were ordered to halt.
The animal results were striking. Mice and ferrets successfully grew new, fully functional teeth without adverse effects. Ferrets were chosen specifically because their dental anatomy is closer to human anatomy than mice. Single-antibody administration produced complete teeth that integrated with the surrounding dental structures. Those results were published in a 2021 peer-reviewed study and formed the scientific foundation for moving into human testing.
Toregem BioPharma’s anti-USAG-1 antibody was designated an orphan drug by Japan’s Ministry of Health, Labour and Welfare on September 29, 2025, for severe congenital oligodontia – a rare condition in which many teeth never form. Orphan drug status comes with accelerated regulatory review, reduced fees, and priority access to government funding. That designation indicates Japanese regulators view this research as clinically urgent.
Who Is Behind the Drug
Takahashi co-founded Toregem BioPharma, a Kyoto University spin-off established in May 2020, to bring this research into clinical development. According to Toregem’s news page, the company has raised approximately USD 5.3 million in Pre-Series C financing, with total past funding – including grants and subsidies – now exceeding USD 29 million.
In June 2024, Japan’s Agency for Medical Research and Development selected TRG-035 – the drug’s official name – for its FY 2024 Venture Ecosystem Enhancement Project for Drug Discovery, providing funding and strategic guidance. The drug is delivered via intravenous injection, entering the bloodstream and targeting USAG-1 systemically rather than through any topical or surgical application to the teeth.
TRG-035 is also being developed in partnership with WuXi Biologics, a global biologics contract research, development, and manufacturing organization. The two companies signed an MOU to form a strategic partnership for TRG-035 development, under which WuXi Biologics provides integrated CMC services and supports Toregem’s IND application for the drug.
The Human Trial Now Underway
In October 2024, researchers at Kyoto University Hospital commenced human trials for TRG-035, the experimental drug designed to stimulate new tooth growth by targeting the USAG-1 protein.
The initial phase enrolls 30 healthy adult males aged 30 to 64, each missing at least one tooth. The primary goal is to assess safety and determine appropriate dosing. Phase I trials are not designed to prove efficacy – they are designed to confirm the drug does not harm, and to identify the right dose for future testing. Early-phase human trials have shown no severe side effects to date.
If successful, subsequent phases will focus on children aged 2 to 7 with congenital anodontia – a condition where individuals are born without a complete set of teeth, affecting approximately 1% of the population. Dental implants require a fully developed jaw, making them unsuitable for young children, and dentures in toddlers carry serious developmental concerns. A drug that could stimulate natural tooth growth from existing dormant buds would address a clinical gap that currently has no adequate solution.
The research team’s longer-term goal reaches beyond rare congenital conditions. Although TRG-035 is being developed for congenital hypodontia, Toregem BioPharma plans to investigate its use in acquired tooth loss. Injuries, aging, and periodontal disease cause millions of adults to lose teeth every year, and if the drug proves effective in those cases, it could reduce the need for dental implants.
Why Tooth Regeneration Matters Beyond the Lab
The American College of Prosthodontists reports that over 120 million Americans are missing at least one tooth, and approximately 36 million have lost all of their natural teeth. According to the CDC, about 11% of adults aged 65 to 74 and 20% of those aged 75 and older have lost every tooth.
The CDC identifies the leading causes of tooth loss as cavities, periodontitis (chronic gum disease with accompanying bone loss), and smoking – meaning most tooth loss is tied to conditions that are often preventable but frequently go unmanaged until the damage is irreversible. Current replacement options – implants, bridges, and dentures – address the functional gap, but none restore living tissue.
A tooth grown from the body’s own dormant buds would have roots, blood supply, nerve connections, and enamel – a real tooth in every biological sense, not a titanium post in a drilled-out socket. That is the fundamental difference between what TRG-035 aims to do and what every existing dental replacement achieves.
What the Timeline Actually Looks Like
Researchers aim for a potential release of the tooth regeneration drug around 2030, pending the outcomes of ongoing and future trials. For a drug that has just entered Phase I safety testing, that target requires each subsequent trial phase to proceed without major complications – a sequence that has historically taken longer than projected.
After the adult male safety cohort, the next phase moves to children with congenital anodontia, testing whether the drug can stimulate growth in people who lack a full complement of tooth buds. After that, researchers plan to test in adults with partial tooth loss from decay, trauma, or gum disease – the largest potential patient group by far.
Further trials will need to establish how durable regenerated teeth are, how safe the treatment is long-term, and how well it works across different patient groups. Animal studies and early human safety data are encouraging, but they do not yet indicate whether a drug-induced third tooth holds up under decades of chewing, or whether the treatment performs equally well across different jaw structures or health conditions.
TRG-035 is currently being developed for people who are missing teeth due to congenital conditions, not as a general elective procedure. The orphan drug designation, specifically tied to congenital tooth agenesis, reflects that priority. Whether TRG-035 eventually becomes available for tooth loss from ordinary decay or injury depends on the results of trials that have not yet started.
What to Do Now
For the 120 million Americans currently living with tooth loss, TRG-035 is not yet an option. It is in human trials, with a 2030 target date contingent on favorable results from multiple additional phases of testing. The most effective tools available now focus on preventing the tooth loss that makes regeneration necessary.
Periodontal disease and decay cause millions of adults to lose teeth every year, and most of those losses are preceded by warning signs: bleeding gums, sensitivity, loosening teeth. Regular dental check-ups catch gum disease and decay early enough to treat them before extraction becomes necessary. The CDC identifies cavities, periodontitis, and smoking as the primary drivers of tooth loss, which means quitting smoking, consistent flossing, and professional cleanings at least twice a year remain the most effective preventive measures available.
If you are already missing teeth and exploring options, ask your dentist about clinical trial eligibility – depending on your age, the number of missing teeth, and your location, you may qualify for future phases of the Toregem research. Animal studies demonstrated successful tooth regeneration, and early human safety testing has produced no serious adverse events to date. Whether growing third teeth through this drug becomes a standard dental treatment depends on what the next several years of trials reveal – but the research is real, the drug exists, and the first humans have already received it.
Disclaimer: This information is not intended to be a substitute for professional medical advice, diagnosis, or treatment and is for information only. Always seek the advice of your physician or another qualified health provider with any questions about your medical condition and/or current medication. Do not disregard professional medical advice or delay seeking advice or treatment because of something you have read here.
AI Disclaimer: This article was created with the assistance of AI tools and reviewed by a human editor.