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OSAKA, Japan — In a move that could render dental implants and dentures obsolete, researchers at Kyoto University Hospital have launched the world’s first human clinical trials for a drug designed to regrow teeth. The medication, known as TRG-035, targets a specific protein that prevents a “third set” of teeth from budding in humans. If successful, this regenerative therapy could be available to the public as early as 2030, marking the most significant advancement in dentistry since the invention of the dental implant in the 1960s.
The Phase 1 trials, which began in late 2024 and are currently ongoing as of May 2026, involve 30 healthy male volunteers aged 30 to 64. Each participant is missing at least one molar. The primary objective of this initial phase is to establish the safety of the intravenous drug and determine the appropriate dosage before moving to more complex patient populations.
The Science of the “Third Set”
Most humans develop two sets of teeth in their lifetime: primary (baby) teeth and permanent teeth. However, scientists have long known that humans possess the genetic “buds” required to grow a third set. In nature, these buds remain dormant, suppressed by a protein called USAG-1 (Uterine Sensitization-Associated Gene-1).
USAG-1 acts as a molecular brake, inhibiting Bone Morphogenetic Protein (BMP) signaling—a critical pathway for tooth and bone formation. TRG-035 is a monoclonal antibody specifically engineered to neutralize USAG-1. By temporarily lifting this biological brake, the drug allows the body’s natural regenerative processes to take over, reactivating dormant tooth buds to grow fully functional, natural teeth integrated directly into the jawbone.
“We knew that the genetic ability was there,” says Dr. Katsu Takahashi, lead researcher and head of dentistry at the Medical Research Institute Kitano Hospital. “The challenge was finding the right ‘key’ to unlock it. After decades of research, TRG-035 appears to be that key.”
The path to human trials was paved by a series of successful animal studies. In a landmark 2021 study published in Scientific Reports, Dr. Takahashi’s team demonstrated that blocking USAG-1 allowed mice with congenital tooth agenesis (a condition where teeth fail to develop) to grow new teeth. Subsequent tests on ferrets—which share a similar dental pattern to humans—and dogs confirmed that the new teeth were structurally sound and functional.
From Bench to Bedside: The Clinical Roadmap
The development of TRG-035 is being managed by Toregem Biopharma, a venture-backed startup born out of Kyoto University. The current 11-month Phase 1 trial monitors how the drug moves through the human body (pharmacokinetics) and checks for any adverse side effects on bone density or other organs.
Following the completion of Phase 1, the researchers have a structured timeline:
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2027 (Phase II): Trials will expand to children aged 2 to 7 who suffer from congenital anodontia (the absence of all or some teeth from birth). This condition affects roughly 0.1% to 1% of the global population.
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2029 (Phase III): Large-scale trials involving older adults who have lost teeth due to environmental factors like decay or injury.
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2030: Targeted commercial release, pending regulatory approval from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) and the U.S. Food and Drug Administration (FDA).
Expert Commentary: Revolutionary, but Proceed with Caution
The global dental community is watching the Japanese trials with a mix of awe and professional scrutiny.
“This approach is amazing and promising,” says Professor Angray Kang, a molecular scientist at Queen Mary University of London. “Activating the body’s own natural regeneration pathways is the holy grail of restorative medicine.”
Dr. Chengfei Zhang, a specialist in dental regenerative medicine, notes that biological teeth offer a distinct advantage over current prosthetics. “Implants are effective, but they lack the periodontal ligament that allows natural teeth to sense pressure and integrate with the jaw’s natural movement. A regrown tooth is, quite literally, the perfect fit.”
However, independent experts warn that the transition from mice to men is fraught with challenges. A 2026 review in Clinical and Experimental Dental Research points out that because USAG-1 also plays roles in bone metabolism elsewhere in the body, researchers must prove that TRG-035 won’t cause unintended bone growth or “off-target” effects in other organs.
Addressing a Global Health Crisis
The implications for public health are staggering. According to the World Health Organization (WHO), nearly 3.5 billion people worldwide are affected by oral diseases. Severe periodontal disease and untreated caries often lead to total tooth loss (edentulism), which affects approximately 350 million people globally.
In regions like India, where over 90% of adults report dental issues, the lack of access to affordable care means many live with missing teeth for decades. Current solutions are often cost-prohibitive; a single dental implant in the U.S. or Europe can exceed $3,000.
“Imagine a farmer in a rural area like Mandi, Himachal Pradesh,” says Dr. Takahashi. “Currently, if they lose a tooth, they may struggle with ill-fitting dentures for life. In the future, a single series of injections could allow them to grow their own tooth back within months.”
Beyond the physical benefits, the economic impact is significant. Global dental healthcare costs are estimated at $500 billion annually. By reducing the need for invasive surgeries and lifelong prosthetic maintenance, TRG-035 could substantially lower the long-term financial burden on both patients and healthcare systems.
The Road Ahead: Hurdles and Expectations
While the 2030 goal is ambitious, several hurdles remain. One primary concern is hyperdontia—the risk of growing too many teeth or teeth in the wrong places. In animal trials, researchers had to calibrate the dosage carefully to ensure only the intended teeth regrew.
Additionally, the current trials are limited in demographic scope, focusing primarily on Japanese male participants. Expanding these trials to include diverse ethnic backgrounds and genders will be essential for global FDA approval.
Despite these challenges, the momentum is undeniable. For the millions of people currently relying on bridges and dentures, the prospect of a “third set” of teeth is no longer the stuff of science fiction—it is a clinical reality currently being tested in a hospital in Osaka.
References
- https://health.economictimes.indiatimes.com/news/industry/scientists-develop-a-regenerative-therapy-that-may-bring-back-teeth/130969515?utm_source=latest_news&utm_medium=homepage
Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.
