Originally published 2022-07-03.
Can a drug make teeth repair themselves? In mice, at least partly, yes. In a study published in Scientific Reports in January 2017, a team at King's College London led by Professor Paul Sharpe drilled small holes into the molars of mice, capped them with a tiny collagen sponge soaked in a drug called tideglusib, and watched the teeth lay down new dentine until the damaged area was filled. Within six weeks the sponge had dissolved and natural tooth tissue had taken its place.
Tideglusib had previously been tested in people as a possible treatment for Alzheimer's disease, which is why headlines called it an "Alzheimer's drug". The real story is more modest and more interesting: it is not a cure for cavities you can buy, and it does not grow a whole new tooth. It is a proof of concept that the tooth's own repair system can be switched up.
What the researchers actually did
The team, Vitor Neves, Rebecca Babb, Dhivya Chandrasekaran and Paul Sharpe, worked with the upper first molars of mice. Using a fine dental burr, they cut through the enamel and dentine to expose the pulp, the soft living tissue in the centre of the tooth. They then placed one of several fillings on the injury and sealed it with a standard glass ionomer cement:
- a collagen sponge soaked in one of three drugs that block an enzyme called GSK-3 (tideglusib, CHIR99021 or BIO);
- a sponge with no drug;
- MTA (mineral trioxide aggregate), a cement dentists already use to protect exposed pulp;
- or the sealing cement alone.
The sponge, sold as Kolspon, is made from fish collagen and is already approved for clinical use. It was chosen because it releases a drug quickly and then breaks down, leaving room for new tissue.
What they found
After four and six weeks the teeth were scanned with micro-CT and examined under the microscope. All three drugs produced markedly more new mineral than the controls, on average about twice as much as the empty sponge and around 1.7 times as much as MTA. By six weeks the injury sites treated with the drugs were filled with dense reparative dentine, and the pulp underneath was still alive. Teeth sealed with cement alone produced none.
The difference from MTA matters to dentists. MTA and similar calcium silicate cements stay in the tooth permanently, and the dentine they encourage tends to form inside the pulp chamber rather than at the site of the damage. The sponge, by contrast, disappeared and was replaced by the tooth's own tissue. In a statement released with the paper, Sharpe said that using a drug already tested in Alzheimer's trials "provides a real opportunity to get this dental treatment quickly into clinics."
How the drug wakes up tooth stem cells
Dentine is the hard, yellowish layer that makes up most of a tooth, beneath the enamel. It is about 70 percent mineral, mostly hydroxyapatite, with collagen and water making up the rest. It is produced by cells called odontoblasts, which line the edge of the pulp.
Teeth are not completely passive. Throughout life they make small amounts of new dentine, and when decay or wear threatens the pulp they produce a protective layer called tertiary dentine. If the original odontoblasts survive, they make "reactionary" dentine. If they die, stem cells in the pulp can turn into new odontoblast-like cells and make "reparative" dentine. The trouble is that this natural response is weak: it can seal a tiny exposure, but not fill a real cavity.
That is where GSK-3 comes in. The enzyme acts as a brake on Wnt signalling, a chemical pathway that tells stem cells to multiply and specialise after injury. Normally GSK-3 tags a protein called beta-catenin for destruction. Block GSK-3, and beta-catenin builds up, enters the cell nucleus and switches on repair genes. In the study, pulp cells exposed to the drugs showed about three times more activity of a marker gene, Axin2, within 24 hours.
Why an Alzheimer's drug?
GSK-3 is also involved in the build-up of tau protein tangles in the brain, which is why tideglusib was tested against Alzheimer's disease and a related condition, progressive supranuclear palsy. It was given to patients by mouth in clinical trials, but development for both conditions was stopped around 2011 to 2012 because it did not work well enough. Older versions of this story described it as a "commonly used" Alzheimer's medicine; that is not correct, as it was never approved for Alzheimer's.
The failed trials still had value for dentistry. They produced human safety data, and a dental filling would use a tiny dose applied directly to the tooth rather than a daily pill. That could make it easier, though not automatic, to move into human dental studies.
The limits: what this study did not show
It is easy to oversell a result like this, so the caveats are worth spelling out:
- It was in mice. Groups were small, from six to nine teeth per time point, and the follow-up lasted six weeks. The authors also noted that the study was not blinded or randomised.
- The holes were tiny. The injuries were about 0.14 mm across, far smaller than a typical human cavity.
- It repaired dentine, not enamel. Enamel is made by cells that are lost once a tooth erupts, so it cannot regrow this way. A treated tooth would still need a covering on top.
- It does not grow new teeth. The drug helps a living tooth patch damage near the pulp; it cannot replace a lost tooth.
In 2023, the King's College group published further work in the Journal of Dental Research reporting that the approach could repair much larger areas of dentine damage and that the new tissue was chemically similar to natural dentine. As far as published reports show, it has not yet been tested in human patients.
What it means for your teeth today
For now, nothing changes at the dentist. Fillings, root canal treatment and pulp-capping cements such as MTA remain the standard, and no tideglusib-based dental product is on the market. If you have a sensitive or damaged tooth, the right step is to see a dentist rather than wait for a future treatment.
The best ways to protect dentine are also the oldest ones: brushing twice a day with fluoride toothpaste, cutting down on sugary snacks and drinks, and getting small cavities treated early, before they reach the pulp. Should regenerative fillings ever reach clinics, they will work best on teeth that still have healthy, living pulp, which is one more reason not to put off check-ups.
The bigger picture is encouraging. Instead of drilling out decay and replacing it with man-made material, dentistry may one day nudge teeth into healing themselves. The 2017 mouse study was one of the first clear demonstrations that this is possible.
Sources: Neves et al., Scientific Reports (2017): Promotion of natural tooth repair by small molecule GSK3 antagonists; Wikipedia: Tideglusib; Wikipedia: Dentin; Freethink: New evidence that teeth can fill their own cavities (2023); original reporting via IFLScience.
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