J-STORIES | 日本発の革新的な挑戦を世界に伝えるメディア

J-STORIES - The conventional way to help people who have lost teeth due to tooth decay or aging has been to replace the missing teeth with dentures or implants. Now Japanese researchers are working on a world-first drug that could help patients grow completely new teeth.

This is the plan of Kyoto-based startup Toregem Bio Pharma Co., and while still in its teething stages, the company hopes to start phase 1 trials to confirm the safety of the drug as early as July 2024.

Founded on research by Kyoto University's Katsu Takahashi, the company then plans to conduct trials on patients with anodontia, a congenital condition in which some or all permanent teeth are absent, paving the way for the commercialization of the treatment in 2030.

Recovery of congenital missing teeth in a mouse model of edentulism (EDA KO). The right image shows the regenerative effects of a single dose of the USAG-1 neutralizing antibody compared to the control group (left).     Source: Toregem Bio Pharma Co. — Recovery of congenital missing teeth in a mouse model of edentulism (EDA KO). The right image shows the regenerative effects of a single dose of the USAG-1 neutralizing antibody compared to the control group (left). Source: Toregem Bio Pharma Co.

Anodontia affects approximately 1 percent of the population, and is usually treated with dental implants. However, despite the problems with eating and speaking the condition can cause, this is not a suitable solution for children. Toregem hopes that its drug will help such patients, and one day the elderly, too, not to mention those who have lost teeth due to tooth decay and other causes.

Kyoto University researcher Takahashi has been working with colleagues on tooth regeneration for some 30 years. He specialized in oral and maxillofacial surgery at Kyoto University’s Graduate School of Medicine and is currently affiliated with the Medical Research Institute KITANO in Osaka.

Images show how antibodies grow teeth in wild mice. Circled at right are extra teeth produced by a single dose of the USAG-1 neutralizing antibody.     Source: Toregem Bio Pharma Co. — Images show how antibodies grow teeth in wild mice. Circled at right are extra teeth produced by a single dose of the USAG-1 neutralizing antibody. Source: Toregem Bio Pharma Co.

A key moment in the development of the new drug came in 2018 when Takahashi and his team turned their attention to a protein called USAG-1 after having unsuccessfully attempted to grow teeth using a genetically modified virus. They found that mice lacking the gene for USAG-1 do not lose their tooth buds during the early stage of tooth development. Based on this, they gave the mice an antibody that suppresses the function of the USAG-1 protein. The outcome was that the mice were able to grow teeth.

“Without the USAG-1 protein itself we couldn’t make antibodies," Takahashi told J-Stories. "Making that protein was difficult.” The development of that protein was ultimately left with Junichi Takagi of Osaka University's Institute for Protein Research.

Photos show the induction of the third set of primary teeth in ferrets, with the intraperitoneal administration of the USAG-1 neutralizing antibody after birth (center) and postnatal intraperitoneal administration (right), resulting in an extra tooth. The photo at left shows the control group.     Source: Toregem Bio Pharma Co. — Photos show the induction of the third set of primary teeth in ferrets, with the intraperitoneal administration of the USAG-1 neutralizing antibody after birth (center) and postnatal intraperitoneal administration (right), resulting in an extra tooth. The photo at left shows the control group. Source: Toregem Bio Pharma Co.

In May 2020, Takahashi and his colleagues founded Toregem Bio Pharma, which is now headed by dentist Honoka Kiso. In total the company’s drug development team numbers over 100 researchers from Kyoto University, Fukui University, and private companies. The company hopes to start medical trials with children in 2025 and is already working with medical institutions across Japan to recruit participants.

In July 2023, the company raised ¥380 million through a third-party allocation of new shares for purposes that include the manufacture of clinical trial drugs. It is also seeking partnerships with pharmaceutical companies with the aim of commercializing its new drug.