The world’s first drug for dental regeneration begins clinical trials in September

Clinical trials of the world’s first drug for dental regeneration will take place in September at Kyoto University Hospital, Japan. Based on an antibody that deactivates the USAG-1 protein, this compound is primarily aimed at patients born with many or all missing teeth (congenital dental agenesis). Ultimately, the researchers hope to expand the therapy to people who have lost teeth either accidentally or due to infection..

While in a healthy person the number of permanent teeth is strictly limited to 32, it is more (hyperdentia, or supernumerary teeth) or less (dental agenesis) that is congenital in about 1% of the population. Dental agenesis occurs as a result of premature cessation of tooth development and includes hypodentia (the absence of 1 to 5 permanent teeth), oligodontia (the absence of more than 6 teeth) and anodontia (the absence of all teeth).

Although several genes have been identified as responsible for congenital tooth agenesis, research has shown that one protein in particular regulates the formation of new teeth. It is a USAG-1 protein that inhibits the activation of BMPs (bone morphogenetic proteins) and Wnt factors, two signaling molecules required for bone and tooth development.

Experiments have shown that USAG-1 deficiency causes the growth of supernumerary teeth in animal models. Researchers at Kyoto University in Japan then suggested that an antibody against USAG-1 could stimulate the growth of dormant germ teeth in people suffering from dental agenesis. Indeed, although humans were thought to have only two sets of teeth (deciduous and permanent), “dormant buds” of a third subset have recently been discovered.

” We want to do something to help those who suffer from lost or missing teeth. Although there is still no treatment that provides a permanent cure, we believe that people’s expectations for dental growth are high. – Katsu Takahashi, co-author of the study and head of the Department of Oral and Maxillofacial Surgery at Kitano Hospital (in Osaka), explains to The Mainichi media.

Commercialization by 2030?

To confirm their hypothesis, Japanese researchers conducted several tests. in natural conditions on mice and ferrets, the latter of which dates back to last year. The trials assessed the effectiveness and safety of a series of anti-USAG-1 antibodies in stimulating the growth of supernumerary teeth. In particular, the antibodies blocked the interaction of USAG-1 with BMP and Wnt. Result: Lower birth and survival rates were reported for the Wnt pathway in animals, given its involvement in skeletal development starting from the embryonic stage. In contrast, a single injection was sufficient to create a third generation supernumerary tooth for the BMP pathway.

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In collaboration with Japanese startup Toregem Biopharma, the researchers now plan to move into clinical trials. The first stage will take place from September this year to August 2025. The antibody will be administered intravenously to 30 healthy men aged 30 to 64 who are missing at least one tooth. Once the effectiveness and safety of the compound are confirmed, the second phase of trials will consist of administering the drug to children aged 2 to 7 years with congenital hypo- or oligodentia (missing at least 4 teeth).

Primarily aimed at people suffering from oligodentia, a condition that until recently was considered irreversible, the drug could become commercially available as early as 2030. Ultimately, the team also hopes to offer the treatment to people who are missing teeth due to injury or tooth decay. those who want to do without prostheses.