New drug may help re-grow teeth, literally

Japanese scientists succeed to stimulate tooth growth in animal studies.

Upon replacement of the milk teeth with permanent ones, people lose the tooth renewal capability and once a permanent tooth is lost, it’s lost for good.

This could not be the case anymore, according to scientists from two Japanese university. A team from the Kyoto University and the University of Fukui argues in a new study published in Science Advances that an antibody for one gene, uterine sensitization associated gene-1 (USAG-1), is able to stimulate tooth growth in animals. 

Although the normal adult mouth has 32 teeth, about 1% of the population has more or fewer due to congenital conditions. Scientists have explored the genetic causes for cases having too many teeth as clues for regenerating teeth in adults.

The researchers said in a release for Medical Xpress that the molecules behind tooth development were already known and the process of growth too. 

The morphogenesis of teeth depends on the interactions of several molecules including bone morphogenetic protein (BMP) and Wnt signaling, explains Katsu Takahashi, a lead author of the study and senior lecturer at the Kyoto University Graduate School of Medicine.

BMP and Wnt are involved in much more than tooth development. They modulate the growth of multiple organs and tissues well before the human body is even the size of a raisin. Consequently, drugs that directly affect their activity are commonly avoided, since side effects could affect the entire body.

USAG-1 interacts with both BMP and Wnt, and the researchers knew that suppressing it would benefit tooth growth – but they didn’t know whether it would be enough.

The researchers therefore investigated the effects of several monoclonal antibodies for USAG-1. Monoclonal antibodies are commonly used to treat cancers, arthritis, and vaccine development. One of the antibodies was able to disrupt the interaction of USAG-1 with BMP only, without any side effects.

When the researchers experimented with this antibody, they observed that BMP signaling was essential to determine the number of teeth in mice, and a single administration was able to generate a whole tooth. Subsequent experiments showed the same benefits in ferrets.

This discovery is essential, because ferrets have similar dental patterns to humans. As the next step, the scientists intend to test the antibodies on larger animals, such as pigs and dogs.

"Conventional tissue engineering is not suitable for tooth regeneration. Our study shows that cell-free molecular therapy is effective for a wide range of congenital tooth agenesis," Manabu Sugai, another author of the study, was quoted as saying.

The study is the first to show the benefits of monoclonal antibodies on tooth regeneration and provides a new therapeutic framework for a clinical problem that can currently only be resolved with implants and other artificial measures.