TRG-035 Human Trials: Japan Tests First Tooth Regeneration Drug

Japanese researchers have launched the world's first human clinical trials for a drug designed to stimulate natural tooth regeneration. The experimental treatment targets people born without teeth and could offer an alternative to dentures and dental implants.

AI Summary

• Japan launched human trials for TRG-035, a drug that regrows teeth naturally
• It targets the USAG-1 gene, which suppresses third-set tooth development
• If successful, TRG-035 could replace implants and dentures by 2030

Why This Matters to Clinics

Tooth loss is common — but treatment hasn’t changed much in decades.

Most patients still rely on costly implants or uncomfortable dentures. Now, a drug from Japan — TRG-035 — may offer a new, non-invasive way to regrow real teeth.

If it works, clinics could soon offer biological restoration, not just prosthetics.

What Is TRG-035 — And Why It Matters

TRG-035 is a monoclonal antibody developed in Japan that blocks the USAG-1 gene, which normally prevents humans from growing a third set of teeth.

By disabling USAG-1, TRG-035 reactivates dormant tooth buds using the body’s natural BMP and Wnt signaling pathways.

In animal trials involving mice and ferrets, a single injection led to fully formed, functional teeth without serious side effects.

The drug could become a biological alternative to implants or dentures, especially for young patients or those born with congenital tooth loss.

The Research Background

Dr. Katsu Takahashi at the Medical Research Institute Kitano Hospital in Osaka leads the research team behind this development. His work focuses on understanding USAG-1 (uterine sensitization-associated gene-1), a protein that prevents additional tooth growth beyond the normal adult set.

Humans possess dormant tooth buds that could theoretically produce a third set of teeth, but USAG-1 blocks this process. The experimental drug, known as TRG-035, is a monoclonal antibody that neutralizes USAG-1 through intravenous injection.

USAG-1 interferes with both BMP (bone morphogenetic protein) and Wnt signaling pathways, which are necessary for tooth development. Research published in Science Advances in 2021 showed that blocking USAG-1 function could address congenital tooth agenesis in mice.

Animal studies in mice and ferrets demonstrated that a single antibody administration generated complete, functional teeth that integrated with existing dental structures. No serious side effects occurred in these studies.

Who’s Behind It — and What Stage Is It In?

The TRG-035 trials are led by Dr. Katsu Takahashi at Kitano Hospital in Osaka.

The drug is being developed by Toregem BioPharma, a Kyoto University spin-off, and manufactured by WuXi Biologics.

Trial Timeline:

• Phase I began in September 2024 at Kyoto University Hospital
• 30 adult males (aged 30–64) with at least one missing molar
• Focus: safety, dosage, and early side effect profile
• Future phases will test the drug in: Children aged 2–7 with congenital anodontia and patients with partial or acquired tooth loss
• Toregem raised ¥380 million ($2.6M USD) in 2023 and is backed by Japan’s Agency for Medical Research and Development (AMED).

Current Clinical Trials

Human trials began in September 2024 at Kyoto University Hospital. The initial phase involves 30 healthy adult males aged 30-64, each missing at least one molar tooth. This 11-month study focuses on safety and proper dosing.

Future phases will test the drug on children aged 2-7 with congenital anodontia, a condition where people are born without complete sets of teeth. This affects approximately 1% of the global population. Additional phases will target patients with partial tooth loss.

Development Company

Toregem BioPharma, founded in May 2020 as a Kyoto University spinoff, is developing the treatment. CEO Dr. Honoka Kiso leads the company, which has partnered with WuXi Biologics for manufacturing and development.

The project received funding from Japan's Agency for Medical Research and Development (AMED) and raised 380 million yen in July 2023.

Medical Context

Congenital anodontia currently requires treatment with dental implants or dentures, but these options are not suitable for children. Dr. Takahashi stated that "restoring natural teeth definitely has its advantages" compared to current treatments, which are often "costly and invasive."

Health ministry data shows more than 90% of people aged 75 or older in Japan have at least one tooth missing. In Japan alone, an estimated 600,000 people have congenital tooth loss, with 3 million affected by acquired tooth loss.

Current dental treatments have limitations. Dental implants require surgery and cost thousands of dollars. Dentures cause discomfort and need frequent adjustments. Bridges require modification of healthy adjacent teeth. None replicate natural tooth function completely.

Projected Timeline

Researchers aim for general availability by 2030. The development timeline includes Phase I safety trials through 2025, Phase II efficacy trials in children with congenital tooth loss through 2027, and Phase III large-scale trials through 2029.

Dr. Takahashi noted that "while there has been no treatment to date providing a permanent cure, we feel that people's expectations for tooth growth are high."

Expert Opinions

The research represents a shift from conventional tissue engineering approaches. Dr. Takahashi explained that "conventional tissue engineering is not suitable for tooth regeneration. Our study shows that cell-free molecular therapy is effective for a wide range of congenital tooth agenesis."

Professor Angray Kang from Queen Mary University of London described the research as "exciting and worth pursuing" but cautioned that development would not be "a short sprint, but by analogy a set of back-to-back consecutive ultra-marathons."

Dr. Chengfei Zhang from the University of Hong Kong called Takahashi's method "innovative and holds potential" but warned that "outcomes observed in animals do not always directly translate to humans."

Current Treatment Focus

The drug initially targets patients with congenital tooth deficiency, though Dr. Takahashi hopes eventual availability for anyone who has lost teeth due to decay, injury, or other factors.

While human trials continue, traditional treatments remain standard care for tooth loss. The Japanese research suggests potential for more natural, less invasive dental treatment options in the future.

Key Takeaways

• TRG-035 blocks USAG-1 to reactivate natural tooth development
• Human trials are ongoing, with initial safety testing through 2025
• If approved, it could be used for congenital and acquired tooth loss
• General public access is projected around 2030
• This could be the first drug to regenerate real, functional human teeth

FAQs for Clinics and Dental Teams

Can TRG-035 be used in children?

Yes. Later trial phases will include children with congenital tooth agenesis, especially those born without a full set of teeth.

When will the drug be available to patients?

If trials are successful, the earliest estimated release is in 2030 — pending final regulatory approvals.

Does this replace dental implants?

Not yet. TRG-035 may be used in specific cases of early-stage or congenital tooth loss. Implants will still be common for many patients.

What makes TRG-035 different?

It reactivates natural tooth buds using internal signaling pathways. No surgery, drilling, or prosthetics involved.

Who could benefit the most?

In Japan alone, over 600,000 people live with congenital tooth loss. Millions more have partial acquired tooth loss. The treatment has potential global relevance, including in fast-developing dental markets like the UAE.

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