Development of a new antibody drug to treat congenital tooth agenesis.

Background: This study aimed to develop a therapeutic agent promoting teeth regeneration from autologous tissues for congenital tooth agenesis, specifically for hypodontia (≤ 5 missing congenital teeth, 10% prevalence) and oligodontia (≥ 6 missing congenital teeth, 0.1% prevalence).

Highlight: We studied mice genetically deficient in the USAG-1 protein, an antagonist of BMP/Wnt which forms excessive teeth. We identified USAG-1 as a target molecule for increasing the number of teeth. Crossing USAG-1-deficient mice with a congenital tooth agenesis model restored tooth formation. We produced anti-USAG-1 neutralizing antibodies as potential therapeutic agents for the treatment of congenital tooth agenesis. Mice anti-USAG-1 neutralizing antibodies can potentially rescue the developmentally arrested tooth germ programmed to a certain tooth type. A humanized anti-USAG-1 antibody was developed as the final candidate.

Conclusion: Targeting USAG-1 shows promise for treating missing congenital tooth. Anti-USAG-1 neutralizing antibodies have been developed and will progress towards clinical trials, which may regenerate missing congenital teeth in conditions, such as hypodontia and oligodontia. The protocol framework for a phase 1 study has been finalized, and preparation for future studies is underway.