How much would our health improve if we could replace diseased or decaying teeth? Oral health is no longer regarded as separate from the health of the rest of the body. Growing evidence links gum disease, tooth loss and disruption of the oral microbiome to cardiovascular disease and dementia, although researchers have not established a direct causal relationship.
Bacteria associated with gum disease have even been detected in the brain tissue of some people with Alzheimer's disease. Scientists are therefore placing increasing emphasis on good oral hygiene and regular dental care, not only to preserve teeth but also as an important part of maintaining overall health.
Replacing a tooth lost to gum disease or severe decay is costly, with a single dental implant often running to several thousand dollars before insurance. As a result, the dental implant industry is a rapidly growing market. The European dental implant market was valued at just over $2bn in 2023 and is projected to exceed $3bn by 2030.
Japanese scientists at Kyoto University, in cooperation with Toregem Biopharma, are now developing a drug named TRG035 that could one day reduce the need for implants altogether. Rather than replacing a missing tooth with an artificial one, their experimental drug is designed to stimulate the growth of a new natural tooth.
The treatment is initially being developed for people with congenital tooth agenesis, a rare condition in which one or more permanent teeth never develop, before researchers investigate its potential use in people who have lost teeth through disease or injury.
A Long Road from Lab to Clinic
The pathway to the drug began in 2007, when researchers discovered that mice lacking the USAG-1 gene developed additional teeth. This led the team to hypothesize that blocking the USAG-1 protein with an antibody could stimulate the growth of new teeth in people with congenital or acquired tooth loss.
After successfully testing anti-USAG-1 antibodies in mice, the researchers developed a humanized version of the antibody. It stimulated tooth regrowth in both mice and dogs and later produced similar results in ferrets.
Although TRG035 is regarded as one of the most closely watched regenerative medicine therapies, with the potential to generate billions of dollars in annual revenue if successful, the odds remain stacked against it. Around 90% of drug candidates that enter clinical development ultimately fail to reach the market.
Even so, TRG035 has already cleared an important hurdle by progressing to Phase II clinical trials after early studies found its safety profile acceptable for further testing. Phase II will now evaluate both the drug's safety and its effectiveness in a larger group of patients. Toregem Biopharma estimates that, if development continues as planned and the treatment receives regulatory approval, TRG035 could reach the market by around 2030.
A System Prone to Excess
As promising as this new drug appears, it could address a significant unmet medical need and potentially divert billions of dollars away from conventional dental treatments. Fillings, crowns and dental implants are all effective treatments, but none fully replicate the strength, structure and biological properties of natural tooth enamel or of a living tooth anchored in the jawbone.
The cost of restorative dental treatment is substantial, and the likelihood of requiring crowns, root canal treatment or tooth replacement generally increases with age. As Western and East Asian populations continue to age, the demand for such procedures is expected to grow, creating a significant market opportunity for regenerative therapies.
At the same time, dentistry has come under increasing scrutiny over concerns that financial incentives may contribute to overtreatment. Investigations in the United States and elsewhere have uncovered cases in which patients were recommended unnecessary fillings, crowns and other procedures, while researchers have warned that economic pressures in private practice can encourage excessive diagnosis and intervention.
Dental philosophy and practice have also evolved considerably over the past 30 years. Many younger dentists now favor minimally invasive approaches, monitoring early-stage cavities rather than filling them immediately, whereas older generations were generally more likely to intervene at an earlier stage.
