Originally published 2017-11-10.
Tideglusib is an experimental drug once tested for Alzheimer's disease that, in a 2017 study at King's College London, helped mouse teeth rebuild their own dentine. Researchers placed tiny collagen sponges soaked in the drug into small holes drilled in mouse molars. Within six weeks the holes had filled with natural, mineralised dentine and the sponge had dissolved away. It is an intriguing result, but it has not yet led to a treatment for people, and fillings are still very much part of dentistry.
The story spread under headlines claiming an "Alzheimer's drug" would end fillings. Below we look at how teeth repair themselves, what the scientists actually did, one important correction about the drug's history, and what would need to happen before this reaches a dental chair.
How teeth repair themselves, and where they fall short
A tooth has three main layers. The hard white enamel on the outside cannot regrow once it is lost. Beneath it lies dentine, a bone-like tissue that makes up most of the tooth. At the centre sits the pulp, the living core with nerves, blood vessels and a population of stem cells.
When decay or an injury reaches close to the pulp, those stem cells can switch on and lay down a fresh layer of so-called reparative dentine. It is the tooth's built-in defence. The trouble is scale: the natural response produces only a thin bridge of new tissue, nowhere near enough to fill the deep cavity that decay usually leaves. That is why dentists clean out the damage and fill the space with man-made materials such as amalgam, composite resin, glass ionomer or calcium-silicate cements.
Those materials work well, but they do not become part of the tooth. Fillings can wear, leak at the edges or fail over time, and a heavily restored tooth may eventually need a crown or root treatment. A way to make the tooth heal itself would be a real step forward.
The science: switching off a molecular brake
The King's College team, led by Professor Paul Sharpe of the Dental Institute, focused on a signalling route inside cells called the Wnt pathway, which helps control how stem cells grow and specialise. An enzyme named glycogen synthase kinase 3 (GSK-3) acts as a brake on that pathway.
Block GSK-3, and the Wnt signal stays switched on for longer. The researchers reasoned that this might push pulp stem cells to keep producing dentine well beyond their usual thin layer. Tideglusib is a GSK-3 inhibitor, and so are two laboratory compounds the team also tested, BIO and CHIR99021.
What the King's College London study did
The results were published in Scientific Reports in January 2017 by Vitor Neves, Rebecca Babb, Dhivya Chandrasekaran and Paul Sharpe. In outline:
- In adult mice, the researchers drilled into an upper molar to expose the pulp, creating a small, cavity-like injury.
- They placed a piece of biodegradable collagen sponge, already approved for clinical use, soaked in a low dose of one of the GSK-3 inhibitors into the hole, then sealed it.
- For comparison, other teeth received a plain sponge, a standard calcium-silicate material (MTA) or glass ionomer.
- They examined the teeth with micro-CT scans and under the microscope after four and six weeks.
Teeth treated with the inhibitors formed about twice as much new mineral as those given a sponge alone, and more than those treated with MTA. By six weeks, dense reparative dentine had filled the injury, the pulp was still alive, and the collagen sponge had been replaced by new tooth tissue. In other words, the scaffold did its job and then disappeared.
Sharpe told The Telegraph that using a drug already tested in people "provides a real opportunity to get this dental treatment quickly into clinics."
A correction: tideglusib is not an approved Alzheimer's drug
Many reports called tideglusib "an Alzheimer's drug". That is slightly misleading. It was developed and tested in clinical trials as a possible treatment for Alzheimer's disease and for progressive supranuclear palsy, but those trials were stopped around 2011 and 2012 because the drug did not show enough benefit. It has never been approved to treat dementia.
The useful part, from the dental team's point of view, is that those trials generated safety data in humans. The doses used inside a tooth are tiny compared with the oral doses taken in the brain studies, which the authors argued should make safety approval simpler. That is a reasonable hope, though a new use in a new tissue still needs its own testing.
Why fillings are not obsolete yet
Mouse teeth are small, and the holes in this study were a fraction of a millimetre across. The authors themselves estimated that a typical human lesion would require roughly ten times more reparative dentine. Follow-up work by the same group reportedly tested larger injuries in rats, but so far no large human clinical trial has shown that tideglusib-soaked sponges can repair real cavities in patients.
There are other limits too. The method depends on living pulp, so it would suit deep cavities that have not yet killed the nerve rather than teeth that already need root canal treatment. Enamel still cannot be regrown, so the outer surface of a repaired tooth would still need a protective seal. The original study was also small and not blinded, which is normal for early research but means results need confirmation.
What this means for your teeth today
Regenerative dentistry is an active field, and GSK-3 inhibitors are one of its more promising leads. Until treatments are proven in people, the best way to avoid fillings is still prevention:
- Brush twice a day with a fluoride toothpaste and clean between your teeth.
- Limit how often you have sugary foods and drinks, especially between meals.
- Visit a dentist regularly so that early decay can be caught while it is still small or reversible.
- If you have tooth pain or sensitivity, see a dentist or talk to a doctor rather than waiting.
The tideglusib story is a good example of drug repurposing: a compound that disappointed in one disease found an unexpected second life in the lab. Whether it becomes a routine dental treatment will depend on careful human trials still to come.
Sources: Neves et al., Scientific Reports 2017; Wikipedia: Tideglusib; The Telegraph (2017); ScienceAlert; Futurism.
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