Tooth Regrowth Drug Moves Closer to Clinical Trials

The first drug intended for tooth regrowth is set to enter clinical trials in July 2024, as a single dose was enough to generate the whole tooth in mice.

The trial led by the Medical Research Institute Kitano Hospital, Japan, will focus on people who lack a full set of adult teeth due to congenital factors. The researchers hope to deliver the therapeutic drug to patients by 2030.

A 2021 study that appeared in Science Advances found that an antibody for one gene — uterine sensitization associated gene-1 (USAG-1) — can stimulate tooth growth in mice with tooth agenesis.

Tooth agenesis is a rare condition in which one or more teeth are missing, affecting between 2.2 to 10.1% of the global population.

The researchers explain that growth of individual teeth depends on the interactions of several molecules, including bone morphogenetic protein (BMP) and Wnt signaling, a pathway that regulates crucial aspects of cell proliferation.

As BMP and Wnt regulate the growth of multiple organs and tissues even before a baby is born, drugs that directly target their activity are usually avoided because side effects could affect the entire body.

Therefore, the researchers focused on the gene USAG-1, suppression of which was known to benefit tooth growth. They investigated how USAG-1 is affected by different monoclonal antibodies that are commonly used to treat cancers, arthritis, and vaccine development.

Because USAG-1 interacts with both BMP and Wnt, several of the antibodies led to poor mice birth and survival rates. However, one antibody disrupted the interaction of USAG-1 with BMP only.

Experiments with this antibody revealed that BMP signaling is essential for determining the number of teeth in mice. Moreover, a single administration was enough to generate tooth regrowth. Later experiments showed the same benefits in ferrets which have similar dental patterns to humans.

If successful, the medication could revolutionize the field of dentistry.

Katsu Takahashi, lead researcher and head of the dentistry and oral surgery department at the Medical Research Institute Kitano Hospital, told The Mainichi, a Japanese newspaper: "In any case, we're hoping to see a time when tooth-regrowth medicine is a third choice alongside dentures and implants."

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