Most people lose a tooth and accept it as a permanent loss. You visit the dentist, explore your options, and leave having been told you have two choices: an implant or a denture. The idea that a missing tooth could simply grow back, the way a lizard regrows its tail, has seemed like exactly the kind of fantasy that belongs in a science fiction novel, not a clinical trial. But that assumption is being quietly challenged in a hospital in Kyoto, Japan, where something genuinely unprecedented is now underway.
The concept itself is not new. Researchers have spent decades asking why humans stop at two sets of teeth. Most other vertebrates keep going, producing fresh teeth throughout their lives. Something in our biology calls a halt after those baby teeth fall out and the permanent set comes in. The question that consumed one Japanese scientist for more than thirty years was whether that halt could be reversed, not through surgery or prosthetics, but through a single drug that tells the body to do what it already knows how to do.
That drug now has a name. It has a company behind it. And as of late 2024, it has human volunteers.
What the Tooth Regrowth Drug Actually Does
Scientists developed TRG-035, an experimental human monoclonal antibody designed to target a protein called USAG-1. A monoclonal antibody, in plain terms, is a lab-engineered protein that acts like a precision-guided key, designed to attach to one specific molecular lock in the body and block it.
The lock it’s blocking, USAG-1, is the reason most of us never grow a third set of teeth. USAG-1 is a bifunctional protein that antagonizes BMP and Wnt, the two signaling molecules essential for tooth development. BMP (bone morphogenetic protein) and Wnt are both biological signals that, when active, instruct the body to build teeth. USAG-1 acts as an off switch, keeping those signals suppressed. When researchers block USAG-1, those developmental signals can flow again.
This finding, confirmed in a landmark 2021 paper published in Science Advances, showed that blocking USAG-1 function through USAG-1 knockout or anti-USAG-1 antibody administration relieves congenital tooth agenesis caused by various genetic abnormalities in mice. In other words, animals that were genetically destined never to grow certain teeth actually grew them when the USAG-1 protein was blocked. That result moved the science from interesting to urgent.
Decades of Research Leading to One Trial
Dr. Katsu Takahashi, head of dentistry and oral surgery at the Medical Research Institute of Kitano Hospital in Osaka, has been working on this problem for nearly three decades. His research began by studying the genetics of tooth development, a field that was barely mapped in the early 1990s. The turning point came when his team identified what happens to animals that lack USAG-1 entirely: in 2007, his team discovered a mouse model with an unusual characteristic – more teeth than normal. That 2007 paper, co-authored by Takahashi and colleagues, documented how USAG-1 abrogation caused rudimentary incisors to survive and erupt as supernumerary (extra) teeth.
That extra-teeth mouse was not a curiosity. It was a proof of concept. If removing USAG-1 from mice produced bonus teeth, then blocking USAG-1 with a drug in animals, or eventually in humans, might do the same. Before moving to human trials, researchers conducted extensive animal studies. These trials involved mice, ferrets, and dogs. The initial studies focused on mice due to their well-studied genetic makeup and shorter life cycles, and researchers observed successful tooth growth with no significant adverse effects. Following promising results in mice, the drug was tested on ferrets, which were chosen because their dental structure closely resembles that of humans. The outcomes showed new teeth developing effectively.
To bring those findings out of the lab, Toregem BioPharma was established. According to Toregem’s official website, the company was founded as a startup spun out of Kyoto University, built on years of Dr. Takahashi’s research.
Inside the Human Trial
The Phase I human trial that began in October 2024 is being conducted at Kyoto University Hospital and is designed to answer the most fundamental question first: is this safe? Phase I trials, for readers unfamiliar with how drug development works, are primarily about safety rather than effectiveness. Researchers aren’t yet trying to prove the drug works in humans. They’re establishing that it doesn’t cause harm and figuring out the right dose.
The initial phase involves 30 healthy adult males aged 30 to 64, each of whom is missing at least one tooth. The primary goal is to assess the safety of the drug and determine the appropriate dosing. The drug is administered intravenously, meaning it’s delivered through an IV rather than as a pill or a topical gel applied to the gums.
As of early 2026, the news from that trial has been cautiously encouraging. According to reporting from Kantenna, a Phase I safety study run from late 2024 through 2025 on adult men aged 30 to 65 missing at least one molar has already wrapped its data collection. As of early 2026, no serious adverse events had been reported, and the final report is due around May.
That’s a meaningful milestone. No serious adverse events at Phase I doesn’t mean the drug works, but it does mean the research can keep moving forward without the kind of safety signal that ends trials before they begin.
A Regulatory Boost That Changes the Timeline
Beyond the trial itself, a significant regulatory development occurred in September 2025. According to Toregem’s official press announcement, the investigational anti-USAG-1 antibody TRG-035 was designated as an orphan drug by Japan’s Ministry of Health, Labour and Welfare for the treatment of severe congenital hypodontia, a rare condition in which people are born missing six or more permanent teeth.
Orphan drug designation is not just an honorary label. The Ministry granted TRG-035 this status because it targets a rare disease with no effective treatment. The designation provides several benefits, including tax incentives, financial aid, reduced regulatory fees, and priority review. Together, these advantages will help speed up the drug’s development and shorten the timeline for patient access.
Separately, in November 2025, Toregem received feedback from a pre-IND (Investigational New Drug) meeting with the US FDA, as confirmed by a formal announcement on Toregem’s website. This is an early step toward parallel American trials. An IND application is what a company files with the FDA before it can begin testing a drug in US patients. Receiving feedback from a pre-IND meeting means Toregem is actively pursuing a US pathway, not just a Japanese one.
Why This Matters for So Many People
According to the CDC’s oral health fact sheet, one quarter of adults aged 65 or older in the United States have 8 or fewer teeth, and more than 1 in 7 adults aged 65 or older have lost all their teeth. Tooth loss at that scale is not just a cosmetic problem. Severe tooth loss limits the ability to chew meat, fruits, and vegetables, and carries real implications for overall nutrition and quality of life.
Even among working-age adults, Americans aged 20 to 64 have an average of just 26 remaining teeth out of a full set of 32. Missing teeth are the norm for a large portion of the adult population, not the exception.
The current options for replacing a missing tooth, implants and dentures, are functional but come with real limitations. Implants require surgery, a recovery period, and a significant cost. Dentures are removable and can be uncomfortable. Neither option gives you back a living tooth. TRG-035, if it works, would.
You can read more about other approaches researchers are pursuing in the area of regenerative dental science, including earlier stem-cell-based methods that showed promise in animal models.
The Deeper Biology: Why We Have a Third Set to Unlock
One of the most surprising aspects of this research is what it reveals about human biology. The conventional understanding has long been that humans simply have two sets of teeth: baby teeth and permanent teeth. But that picture turns out to be incomplete.
There is evidence that dormant buds of a potential third set of teeth exist beneath human gums, sitting quiet and suppressed by proteins like USAG-1. Evidence for this comes partly from a phenomenon called hyperdontia. About 1 in 100 people grow extra teeth beyond their normal set, and a portion of those cases appear to stem from a partially activated third set.
Congenital anodontia, the condition where people are born without a complete set of teeth, affects approximately 1% of the global population. For these patients, particularly children, the current treatment is dentures, which have to be repeatedly remade as a child’s jaw grows. It’s an imperfect solution for a lifelong condition. Subsequent phases of the TRG-035 trials will focus on children aged 2 to 7 who suffer from congenital anodontia.
That future phase carries enormous stakes. A drug that could give a child with no teeth a functional set, grown from their own biology, would be a categorically different outcome than a life of fitted dental appliances.
What to Do With This Information Now
If ongoing trials are successful, the earliest estimated release of TRG-035 is around 2030, pending final regulatory approvals. That’s four years away, and a lot has to go right between now and then. Phase II and Phase III trials still need to happen. Those later phases will test whether the drug actually regenerates teeth in humans, not just whether it’s safe. Regulatory agencies in multiple countries will need to review the data. Manufacturing at scale will need to be established.
What you can take from this research right now is less about waiting for a miracle and more about appreciating what it reveals. The biology of tooth regeneration was never completely switched off in humans. USAG-1 has been holding it in check. Researchers now know how to interfere with that mechanism, at least in the lab and in early human testing. Whether that interference will reliably produce healthy, functional teeth in people is the question the next several years of trials are designed to answer.
For anyone currently dealing with tooth loss, or trying to protect the teeth they have, the practical advice remains unchanged: regular dental visits, attentive oral hygiene, and a diet that supports bone and gum health. A tooth regrowth drug showing early promise is not yet a prescription your dentist can write. But the fact that it exists at all, that it has cleared animal studies, earned orphan drug status, passed through a Phase I trial in humans without serious safety signals, and prompted early FDA conversations, means the field has moved further in the past two years than in the previous two decades.
That’s not a reason to wait. It’s a reason to pay attention.
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.
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