A team of Japanese scientists has developed a groundbreaking drug that stimulates the growth of new teeth—the first of its kind in the world.
Dr. Katsu Takahashi, lead researcher, co-founder of Toregem Biopharma, and head of dentistry and oral surgery at the Medical Research Institute Kitano Hospital in Osaka, Japan, has been working on how to induce the growth of new teeth his entire career.
“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,” he said in an article in The Mainichi.
The antibody-based drug targets a protein that inhibits the growth of new teeth from “tooth buds,” and in previous animal experiments, the drug induced the growth of a “third generation” of teeth, in addition to baby teeth and permanent adult teeth.
Sharks and many reptiles have teeth that are continually replaced, and crocodiles replace their teeth more than 40 times throughout their lifetimes, but mammals do not have the same unlimited tooth-replacing abilities. Until recently, it was assumed that humans had only two sets of teeth. However, there is now evidence that humans also possess these tooth buds, which have the potential to become a third set of teeth.
The drug has been used successfully to grow new teeth in mice and ferrets, with clinical trials expected to begin in humans in July 2024 to test the drug’s safety in healthy adults.
In 2018, Dr. Takahashi and his team gave the drug to ferrets, which, like humans, have tooth buds, baby teeth, and permanent adult teeth—and new teeth grew.
In similar experiments in 2018, the team gave the drug to mice, which also grew new teeth, and the findings were published in Science Advances in 2021.
The new drug could solve the problem of tooth agenesis, which is the failure of all or part of an organ to grow during fetal development. Tooth agenesis is the absence of one or more permanent teeth. Oligodontia is the absence of six or more teeth (not including third molars), and anodontia is the complete absence of teeth.
Anodontia is a congenital disorder that affects about 1 percent of the population.
Children born with tooth agenesis have trouble with basic activities such as eating and speaking, which can undermine their development. Until now, treatments have focused on replacing the missing teeth with dentures, bridges, and implants.
If the first clinical trial in healthy adults succeeds, Dr. Takahashi said he and his team are planning a second clinical trial in 2025 for children between 2 and 6 with anodontia. The children will be injected with the drug to stimulate the growth of new teeth.
How the Drug Works
In the early 1990s, scientists began isolating genes that, when removed, caused mice to grow fewer teeth, and researchers found that the number of teeth that grew varied by manipulating just one gene.
In 2005, Dr. Takahashi returned to Japan from studying in the United States. He and his team at Kyoto University began research based on the discovery of the genes that specifically affect tooth growth. They found that mice missing a particular gene had more teeth and that a protein, called USAG-1, which was synthesized by the gene, decreased the number of teeth that grew. They theorized that blocking the USAG-1 protein would stimulate the growth of more teeth. They were right.
Dr. Takahashi and his team developed an antibody medication that could block the protein’s function, testing it in 2018 on mice who congenitally had fewer teeth. The mice were given the drug, and new teeth appeared—it was the first medicine ever to regenerate teeth. The findings were published in 2021.
Final Thoughts
The implications of such a drug could be significant given that dental problems—and tooth loss in particular—affect billions of people worldwide, including the approximately 41 million Americans who have dentures, according to 2020 U.S. Census data and Simmons National Consumer Survey. That’s about 12 percent of the population.
According to Centers for Disease Control and Prevention statistics, 26 percent of adults over 65 have eight teeth or fewer, and 17 percent adults 65 or older have lost all of their teeth—although the numbers have been decreasing in recent years. The statistics also show that older adults who face economic challenges, have less than a high school education, or smoke are more than three times as likely to have lost all their teeth than other groups.
Should the drug prove safe and effective, millions of people worldwide who suffer from a wide range of dental conditions—especially children with congenital disorders—may soon be able to have their teeth grow and develop naturally.
Dr. Takahashi said that he and his team hope to bring the drug to market by 2030.
