⇧ [VIDÉO] You might also like this partner content
Clinical trials of the world’s first tooth regeneration drug will take place in September at Kyoto University Hospital, Japan. Based on an antibody that deactivates a protein called USAG-1, the compound primarily targets patients born with many or all missing teeth (congenital tooth agenesis). Ultimately, researchers hope to extend the therapy to people who have lost teeth accidentally or as a result of infection..
While in healthy humans the number of permanent teeth is strictly limited to 32, it is greater (hyperdontia, or supernumerary teeth) or less (dental agenesis) congenitally in approximately 1% of the population. Dental agenesis results from premature cessation of tooth development and includes hypodontia (absence of 1 to 5 permanent teeth), oligodontia (absence of more than 6 teeth) and anodontia (absence of all teeth ).
While several genes have been identified as responsible for congenital tooth agenesis, studies have suggested that one protein in particular regulates the formation of new teeth. This is the USAG-1 protein, which inhibits the activation of BMP (bone morphogenetic proteins) and Wnt factors, two signaling molecules essential for bone and tooth development.
Experiments have shown that USAG-1 deficiency induces the growth of supernumerary teeth in animal models. Researchers at Kyoto University (Japan) then suggested that an anti-USAG-1 antibody could stimulate the growth of “dormant” germinal teeth in people suffering from dental agenesis. Indeed, while it was believed that there were only two sets of teeth in humans (milk and permanent teeth), the “sleeping buds” of a third subset were recently discovered.
“ We want to do something to help those who are suffering from tooth loss or missing teeth. Although there is no treatment so far that offers a permanent cure, we believe that people’s expectations for tooth growth are high », Explains to The Mainichi media Katsu Takahashi, co-lead author of the study and head of the department of dentistry and oral surgery at Kitano Hospital (in Osaka).
Commercialization by 2030?
To support their hypothesis, the Japanese researchers carried out several tests in vivo on mice and ferrets, the last one dating from last year. The trials evaluated the effectiveness and safety of a range of anti-USAG-1 antibodies in inducing the growth of supernumerary teeth. Specifically, the antibodies blocked the interaction of USAG-1 with BMP and Wnt. Result: the animals recorded lower birth and survival rates for the Wnt pathway, given its involvement in skeletal development from the embryonic stage. In contrast, a single administration was sufficient to generate a third-generation supernumerary tooth for the BMP pathway.
See as well
(A to D) Maxillary incisors of ferrets at different doses of USAG-1 neutralizing antibody administration. (E to G) Computed tomography (micro-CT). (H and I) Immunolocalization of phosphorylated Smad1/5/8 for supernumerary teeth. Arrowheads indicate supernumerary teeth obtained. © A. Murashima-Suginami, Kyoto University
In collaboration with the Japanese start-up Toregem Biopharma, the researchers now plan to move on to clinical trials. The first phase will take place between September this year and August 2025. The antibody will be administered intravenously to 30 healthy men aged 30 to 64, but who are missing at least one tooth. Once the effectiveness and safety of the compound have been confirmed, the second phase of the trials will consist of administering the compound to children aged 2 to 7 years old and presenting with congenital hypo- or oligodontia (at least 4 missing teeth).
Primarily targeting people suffering from oligodontia — a condition until recently thought to be irreversible, the drug could be commercially available as early as 2030. Eventually, the team also hopes to offer the treatment to people who lack it teeth due to injury or cavities, and who wish to do without prostheses.
