Teeth that grow back: Japanese researchers want to make it possible by 2030

There are people who wear their gap teeth like a trademark: actor Jürgen Vogel, for example, did this for years – and currently German star striker Niclas Füllkrug is causing a sensation in the stadium with his tooth gap. Until now, when gaps in teeth occur due to accidents or genetics, the only option was to make the best of it, like Vogel and "Fülle" – or to resort to artificial teeth, bridges and/or crowns to cover up the problem. Japanese researchers now want to tackle the problem medically: with the help of an antibody therapy that switches off a specific gene that has so far prevented teeth from growing back. This should make it possible to generate natural "third teeth", although this seems physically impossible in mammals – once they are gone, they stay gone.

High expectations

A research group made up of scientists from Kyoto and Fukui Universities has been pursuing the idea since 2021. Last summer, it was announced that the first clinical trials would take place. These are now about to start at Kitano Hospital in Kita, Osaka, according to the newspaper, The Mainichi. The "medicine for new tooth growth" is to be tested from September 2024 on 30 otherwise healthy men between 30 and 64 who are missing teeth. The study is to run until August 2025. If all goes well, commercialization is expected by 2030. "We want to do something to help those who suffer from tooth loss or toothlessness," says Katsu Takahashi, Head of Dentistry and Dental Surgery at Kitano Hospital, who has been working on the idea for years. So far, there has been a lack of permanent treatment options for those affected. "People's expectations are [accordingly] high."

Takahashi and his colleagues had previously found antibodies for a gene whose suppression stimulates tooth (re-)growth. The gene in question, whose manipulation in animal experiments already works well in mice and ferrets, is the "Uterine Sensitization Associated Gene-1", USAG-1 for short. "We already knew that the suppression of USAG-1 promotes tooth growth. What we didn't know was whether it would be enough," said Takahashi when he presented the idea three years ago, when he was still a senior lecturer at the Kyoto University Graduate School of Medicine.

No side effects in animal experiments so far

To switch off USAG-1, the researchers examined various monoclonal antibodies. These are otherwise used to produce vaccines or fight certain types of cancer, among other things. As the gene is not only important for the formation of teeth, it was of central importance to find very specific antibodies that only block this one function. USAG-1 also interacts with proteins that play a role in the development of various other human organs, which made the procedure risky. The researchers have now reached a level of safety that allows a clinical phase 1 trial. If freedom from problematic side effects is ruled out, people suffering from genetic edentulism will also be treated - the researchers are thinking of children between the ages of 2 and 7.

The test group will be people who are missing at least one back tooth so that the potential effect can be tested. They will receive the antibodies intravenously. No problematic side effects have been reported in the animal trials so far. Ultimately, Takahashi and his team hope that the therapy will be available to everyone who suffers from tooth loss - including as a result of dental disease or accidents. There are millions of people on the planet who suffer from this and only live with artificial teeth. In many regions of the world, however, there is not enough money for this, as such treatments are expensive. Hereditary tooth loss - or a set of teeth missing from birth - is said to occur in around one percent of the population. As many as 0.1 percent of the population are missing six or more teeth out of a total of 32.

(bsc)