World's 1st 'tooth regrowth' medicine moves toward clinical trials in Japan

Katsu Takahashi, head of the dentistry and oral surgery department at the Medical Research Institute Kitano Hospital, is seen in the city of Osaka's Kita Ward on May 16, 2023. (Mainichi/Mirai Nagira)

OSAKA -- A Japanese research team is making progress on the development of a groundbreaking medication that may allow people to grow new teeth, with clinical trials set to begin in July 2024.

The tooth regrowth medicine is intended for people who lack a full set of adult teeth due to congenital factors. The team is aiming to have it ready for general use in 2030.

In prior animal experiments, the medicine prompted the growth of "third-generation" teeth following baby teeth and then permanent adult teeth.

"The idea of growing new teeth is every dentist's dream. I've been working on this since I was a graduate student. I was confident I'd be able to make it happen," said Katsu Takahashi, lead researcher and head of the dentistry and oral surgery department at the Medical Research Institute Kitano Hospital in the city of Osaka.

A new tooth is seen growing in a mouse treated with the tooth regrowth medicine. (Photo provided by Katsu Takahashi, head of the dentistry and oral surgery department at the Medical Research Institute Kitano Hospital)

Anodontia is a congenital condition that causes the growth of fewer than a full set of teeth, present in around 1% of the population. Genetic factors are thought to be the major cause for the one-tenth of anodontia patients who lack six or more teeth, a condition categorized as oligodontia. These conditions are also known as tooth agenesis. People who grow up with tooth agenesis struggle with basic abilities like chewing, swallowing and speaking from a young age, which can negatively impact their development.

After completing a dentistry degree, Takahashi went on to graduate studies in molecular biology at Kyoto University in 1991. Afterwards, he studied in the U.S.

Around that time, research around the world had begun to pinpoint genes that, when deleted, would cause genetically modified mice to grow fewer teeth. "The number of teeth varied through the mutation of just one gene. If we make that the target of our research, there should be a way to change the number of teeth (people have)," Takahashi said of his thoughts at the time.

The front teeth of a ferret treated with tooth regrowth medicine are seen in a photo provided by Katsu Takahashi, head of the dentistry and oral surgery department at the Medical Research Institute Kitano Hospital. The medicine induced the growth of an additional seventh tooth (center).

It was around 2005, when he delved further into the subject at Kyoto University after returning to Japan, that he began to see a bright path for his continued research. The researchers found that mice lacking a certain gene had an increased number of teeth. A protein called USAG-1, synthesized by the gene, was found to limit the growth of teeth. In other words, blocking the action of that protein could allow more teeth to grow.

Takahashi's research team narrowed their focus onto USAG-1, and developed a neutralizing antibody medicine able to block the protein's function. In experiments in 2018, mice with a congenitally low number of teeth were given medicine that resulted in new teeth coming through. The research results were published in a U.S. scientific paper in 2021, and gained much attention as the beginnings of the world's first tooth regeneration medicine.

Work is now underway to get the drug ready for human use. Once confirmed to have no ill effects on the human body, it will be aimed at treating children aged 2 to 6 who exhibit anodontia. "We hope to pave the way for the medicine's clinical use," Takahashi said.

If successful, a drug to regenerate teeth may be a game-changer for the entire field of dentistry.

Animals including sharks and some reptile species can continuously regrow teeth. It's been assumed that humans only grow two sets of teeth in their lifetime, but in fact, there is evidence that we also have the "buds" for a third set.

Around 1% of the population exhibits the converse of anodontia: hyperdontia, a congenital condition causing a higher-than-normal number of teeth. According to research by Takahashi's team, one in three such cases manifests as the growth of a third set of teeth. Takahashi believes that in most cases, humans' ability to grow a third set was lost over time.

When the researchers applied the drug to ferrets, they grew an additional seventh front tooth. As the new teeth grew in between the existing front teeth and were of the same shape, the medicine is thought to have induced the generation of third-set teeth in the animals.

When treatment of teeth is no longer possible due to severe cavities or erosion of the dental sockets, known as pyorrhea, people lose them and need to rely on dental appliances such as dentures. The ability to grow third-generation teeth could change that. "In any case, we're hoping to see a time when tooth-regrowth medicine is a third choice alongside dentures and implants," Takahashi said.

For further information or inquiries about Takahashi's research, please visit https://www.kitano-hp.or.jp/toothreg/ (in Japanese).