Japanese scientists propose drug to regrow teeth, promise trials won't bite

Adios, dentures?

Japanese researchers plan to begin human trials of a tooth regrowth drug this fall at Kyoto University Hospital following successful animal trials.

The first stage of tests will begin in September and run through 2025 involving 30 adult males. A following round will test the drug on children between the ages of two and seven with a congenital lack of teeth.

"We want to do something to help those who are suffering from tooth loss or absence," lead researcher Katsu Takahashi told Japanese newspaper The Mainichi. "While there has been no treatment to date providing a permanent cure, we feel that people's expectations for tooth growth are high."

The new Miracle-Gro

Regrowing teeth isn't really that far-fetched, and medical researchers have had their eyes on it for years. After all, we know other animals can regrow teeth.

Cheng Ming Chuong, author of a 2013 paper on human tooth regrowth, said a decade ago we should look to alligators to see how regrowing teeth in humans could work. Gators, Chuong said, have teeth that grow in sets of three – and so do humans, for a few months at least.

In alligators, beneath a mature tooth lies a juvenile one, and beneath that lies a stem cell bud that has the potential to become a new tooth.

"When the mature tooth falls out, the second one becomes a mature one, and the stem cell becomes a baby one," Chuong said. "Interestingly, they are able to do this process repeatedly."

Humans have a similar structure, but lack that stem cell bud. According to Chuong, if we could only figure out how to manipulate the molecular pathway involved in disabling additional tooth growth, we could theoretically undo tooth loss.

Enter Takahashi. 

In 2021, his team discovered a gene – uterine sensitization-associated gene-1 (USAG-1) – that appeared to stop the production of additional teeth in mice. Deactivating that same gene and stopping production of the protein it regulates has also caused other animals to grow lost, or even additional, teeth.

With clinical trials on animals out of the way – and no serious side effects to report – Takahashi and his team are ready to try suppressing USAG-1 in humans, once the drug is found safe for human use.

Takahashi and his team have spun up their own company called Toregem Biopharma to commercialize the USAG-1 drug, and hope to have it on the market by 2030. While initial tests are mainly focused on congenital tooth loss, the team hopes teeth lost due to cavities, injury, and other accidents will be regrowable as well. ®

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