What is TRG-035?

TRG-035 is an antibody medicine designed to neutralise USAG-1, a protein that holds back tooth development, with the aim of letting dormant tooth buds grow into new teeth. It is a biologic given by intravenous infusion in trials, not a pill, gel or toothpaste.

A joint press release published through Japan's medical research agency AMED in May 2024 describes TRG-035 as a human anti-USAG-1 antibody, nicknamed the "tooth-growing medicine" in Japan.

How does the TRG-035 tooth regrowth drug work?

The TRG-035 tooth regrowth drug works by blocking USAG-1, a natural brake on tooth formation: in animal studies, switching off this brake increased BMP signalling in the tooth bud, which allowed teeth that would otherwise not form to develop.

USAG-1, BMP and Wnt in plain language

• USAG-1 (uterine sensitization associated gene-1) is a protein that interacts with two growth signalling systems, BMP and Wnt.
• BMP and Wnt are signals that help decide how many teeth form and where. USAG-1 dampens them.
• The antibody sticks to USAG-1 so it can no longer dampen the signal in the tooth bud.

The key paper is Murashima-Suginami and colleagues, "Anti–USAG-1 therapy for tooth regeneration through enhanced BMP signaling", published in Science Advances in 2021. Kyoto University reported that some antibodies tested caused poor birth and survival rates in mice, which the team linked to the wider roles of BMP and Wnt in the body. They therefore chose an antibody that blocks the interaction of USAG-1 with BMP only.

In mice with congenital tooth agenesis, a single dose of that antibody was enough to generate a whole tooth. Similar results were seen in ferrets. These are animal results, not proof that it works in people.

What do the TRG-035 clinical trials involve, and who are they for?

The TRG-035 clinical trials started with a Phase I safety study in healthy adult men missing at least one molar, and the next step is a Phase IIa study in children with severe congenital tooth agenesis; adults who lost teeth to decay or gum disease are not the current focus.

Phase I: safety in healthy adults

The registry entry describes a randomised, double-blind, placebo-controlled study with a single intravenous dose in five escalating steps. It aimed to enrol 30 healthy men aged 30 to 65 at consent who were missing at least one molar. The main outcome was safety; secondary outcomes were how the body handles the drug and whether people form antibodies against it. This phase was not designed to prove that teeth regrow, and no regrowth results have been reported.

Phase IIa: children born with missing teeth

Dentistry.co.uk reports a planned open-label, multicentre Phase IIa study in 24 children with severe congenital tooth agenesis, mainly to study dosing. The AMED release named Kitano Hospital as the planned Phase IIa site and described the target as patients born without six or more teeth, though an appendix to the same release gave a different age and tooth range. Final eligibility details have not yet been published.

When will the TRG-035 tooth regrowth drug be available?

Nobody can give a reliable date: TRG-035 still needs efficacy results, more trials and regulatory approval, and even if those go well, the first approved use would most likely be for congenital tooth agenesis rather than for adults who have lost teeth.

The researchers have said they planned for the medicine to be ready for general use in 2030. Dentistry.co.uk notes that this target should be treated as provisional, because Phase II efficacy data and further review are still needed. We cannot say whether, or when, TRG-035 will reach patients.

Why is TRG-035 not available to patients today?

TRG-035 is not available today because it is still an investigational drug: it has passed only a Phase I safety study, has not shown that it regrows human teeth, has no marketing approval in Japan or elsewhere, and is given only to volunteers inside registered trials.

• No efficacy data yet. Phase I tested safety and dosing, not whether a tooth grows.
• No approval. No regulator has authorised it for sale.
• Open questions for adults. Adults who lost teeth to decay or gum disease may not have a dormant tooth bud in the right place; Toregem lists acquired tooth loss as a longer-term goal, not a current study.

For the wider picture of stem cells, growth factors and tissue engineering, read our overview of regenerative dentistry.

Should you wait for TRG-035 or replace missing teeth now?

For most adults, waiting for TRG-035 is not a sound plan, because there is no confirmed date or proof it will work for acquired tooth loss, while a gap left for years can let neighbouring teeth drift and the jawbone shrink. Replacing a tooth now does not stop you from benefiting from future research.

After a tooth is lost, the bone that held it gradually shrinks because it is no longer stimulated. We explain this in the consequences of losing one tooth and in our guide to preventing jawbone loss.

What can adults missing teeth do now?

Adults missing teeth can choose from four well-established options today: a dental implant for a single tooth, a bridge supported by neighbouring teeth, a removable partial or full denture, or an All-on-X fixed bridge on several implants when a whole arch needs replacing.

Cleveland Clinic lists braces, partial dentures, bridges and implants as treatments for people born with missing teeth.

Dental implants

An implant acts as an artificial root. Cleveland Clinic explains that the bone fuses to it during healing, a process called osseointegration, before the final tooth is fitted. See our single tooth implant guide, or our partner clinic's page on single tooth implants in Istanbul.

Bridges and dentures

A bridge relies on neighbouring teeth; read about dental bridges in Istanbul. Dentures avoid surgery; our guide to full and partial removable dentures explains the choices, and implant-supported dentures combine both.

All-on-X for a full arch

When most teeth in a jaw are missing or failing, All-on-X places a fixed bridge on four or more implants. Our All-on-X dental implants page explains the family, and All-on-4 vs All-on-6 vs All-on-8 compares the versions. Our partner site also has an All-on-X overview.

How do you choose a tooth replacement today? Step by step

Choosing a tooth replacement starts with an examination and 3D X-ray, then a comparison of options based on your bone, gums, bite, health and goals, followed by a written plan with the number of visits and days before any treatment begins.

1. Share photos and X-rays for an online first review; see our online dental consultation.
2. Clinical examination of teeth, gums, bite and general health.
3. 3D CBCT scan to measure bone height and width and locate nerves and sinuses.
4. Compare options: implant, bridge, denture or All-on-X, with honest pros and cons.
5. Written plan and timeline, including healing months between stages.
6. Treatment and follow-up, with remote check-ins after you fly home.

Watch: dental implant treatment step by step

In this one-minute video, Dr. Abdurrahman Öztürk walks through implant treatment at our Istanbul clinic, from the first examination and 3D planning to placement and the final tooth. Whether implants suit you is decided after your examination.

Is TRG-035 safe?

TRG-035 safety is still being studied: Toregem reports that the Phase I trial in healthy adults confirmed the drug's safety, but the full data have not been published or peer reviewed, and safety in children is the subject of the next trial.

Key takeaways: TRG-035

• TRG-035 is an anti-USAG-1 antibody from Toregem BioPharma, based on Kyoto University research led by Dr. Katsu Takahashi, now at Kitano Hospital.
• In mice and ferrets, blocking USAG-1 enhanced BMP signalling and allowed missing teeth to form.
• Phase I in healthy adult men is complete; detailed results are not yet published.
• Phase IIa in 24 children with severe congenital tooth agenesis has cleared PMDA review; no start date is announced.
• Implants, bridges, dentures and All-on-X remain the established options today.

Replacing missing teeth in Taksim, Istanbul: how our clinic helps

The Dr. Abdurrahman Ozturk Dental Clinic in Taksim, Beyoğlu, plans tooth replacement digitally, explains each option in clear English, and keeps in touch on WhatsApp after you return home; we will also tell you honestly if waiting or a simpler option makes more sense.

Clinic location: Gümüşsuyu Mah., Mete Cad., Beyoğlu, Istanbul, a few minutes' walk from Taksim Square.

To see real implant outcomes, browse our partner site's before and after results. Our sister clinic also explains how AI supports planning at AI dental implants in Istanbul. Results vary between individuals.

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Conclusion

TRG-035 is one of the most interesting ideas in dentistry: a medicine that might one day help the body grow a missing tooth. Today it is an experimental antibody that has completed a safety study and is heading into a trial for children born without many teeth. It is not available, its effect in humans is not yet proven and its timeline for adults is unknown. If you are missing teeth now, implants, bridges, dentures and All-on-X are established options. The team at the Dr. Abdurrahman Ozturk Dental Clinic in Taksim is happy to review your case.