News Brief

In October 2024, as reported by Japanese media, a research team headed by Katsu Takahashi at Kyoto University Hospital launched a phase I clinical trial of "TRG035", the world's pioneering tooth regeneration drug in human testing. This 11-month trial will evaluate the drug's safety and efficacy in 30 male participants aged 30 to 64, each with at least one missing tooth, administered through intravenous injection of TRG035. If the trial progresses well, the drug could be introduced for clinical use by 2030, heralding a new era in dental medicine.

From USAG-1 to TRG035

TRG035 was discovered through research on the USAG-1 protein. It was found that USAG-1 inhibits bone morphogenetic protein (BMP) and can induce renal tubular damage, leading to the development of "USAG-1 protein-deficient mice" as an animal model for kidney disease studies. In 2007, Katsu Takahashi's team accidentally found that mice lacking USAG-1 protein developed more teeth than usual. In subsequent years, the team explored the role of USAG-1 in tooth growth and proposed the hypothesis that inhibiting USAG-1 could boost tooth growth by enhancing BMP and Wnt pathways.

Driven by this hypothesis, the research team concentrated on exploring strategies to promote tooth regeneration by suppressing the USAG-1 protein. In 2021, they made a groundbreaking discovery of a monoclonal antibody, TRG035, which can neutralize the USAG-1 protein. TRG035 effectively blocks USAG-1 activity without affecting the animal's growth. Experimental results have shown that disrupting USAG-1 function through USAG-1 knockout or administration of anti-USAG-1 antibodies can ease congenital dental developmental deficiencies in mice caused by various genetic abnormalities. A single TRG035 injection successfully instigated the growth of a completely new tooth in mice, and these new teeth were similar in both morphology and function to normal teeth. Therefore, anti-USAG-1 antibody therapy could represent a promising avenue for tooth regeneration treatment.

Fig. 1 Recovery of tooth defects and full tooth regeneration in EDA1 mutant mice after administration of USAG-1 neutralizing antibody (Murashima-Suginami A., et al. 2021).

To further confirm TRG035's efficacy, the research team selected ferrets, whose dental structure is similar to that of humans, for experimentation. The results indicated signs of extra tooth growth in the ferrets' maxillary incisor region. These additional teeth resembled normal permanent incisors and were located on the lingual side of the permanent teeth. Although the roots were short, they exhibited continuous growth. This outcome demonstrates that TRG035 also has a strong ability to promote tooth regeneration in ferrets.

Fig. 2 Maxillary incisor regeneration in ferrets using USAG-1 neutralizing antibody
(Murashima-Suginami A., et al. 2021).

To sum up, TRG035 has effectively achieved tooth regeneration in experiments with both mice and ferrets, with no side effects reported. Importantly, the USAG-1 protein has a high amino acid homology of up to 97% across species, including humans, mice, and beagles. This high conservation level undoubtedly enhances the anticipation for TRG035's exceptional performance in human clinical trials, potentially heralding groundbreaking innovations in tooth regeneration.

Conclusion

Although tissue engineering approaches are common in regenerative medicine, their application in tooth regeneration has been limited by cost and safety concerns, and no clinically applicable therapies have emerged yet. TRG035 offers a promising new approach to tooth regeneration, with the potential to shift dental care from restorative to regenerative. We look forward to positive outcomes from clinical trials, bringing hope to patients with missing teeth and making tooth regeneration a reality.

About Alta Stomatology

Alta Stomatology is a company that specializes in the research of oral diseases. We provide comprehensive services in the field of oral research, including disease detection, diagnosis, and drug development. In addition, we also offer a series of high-quality products required for oral disease research, such as cell culture media, detection kits, and antibodies.

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