How an Alzheimer’s drug turned tooth regenerator could unlock regenerative medicine

Researchers at King’s College London have found a new use for an Alzheimer’s drug: repairing teeth. Elly Earls meets Professor Paul Sharpe, lead researcher on the study, to find out what implications this surprising discovery has for dentistry and beyond.

A drug that has been used to treat Alzheimer’s disease in clinical trials has been found by researchers at King’s College London (KCL) to have potential for repairing decayed teeth. If they can prove that the drug works on people as well as animal models, dentistry could soon become one of the first big beneficiaries of regenerative medicine.

It all started with a basic study funded by the UK Medical Research Council. A research team at the Dental Institute at KCL were asked to find out which key signalling pathways are switched on when a tooth is damaged and how this leads to the natural repair that occurs. The most important pathway involved in the process, it turned out, was the Wnt signalling pathway. If it could be stimulated, the researchers thought, they may be able to reproduce – and enhance – the tooth’s natural healing mechanisms.

They were in luck. As the Wnt pathway has been of significant interest to the pharmaceutical industry for many years, because of its involvement in diseases including cancer, there were already a number of existing drugs they could test. Even better, the molecule they eventually hit gold with – tideglusib – had previously been used to treat Alzheimer’s disease in clinical trials, meaning its safety had already been proven.

Better than fillings

Using tideglusib, the researchers, led by Professor Paul Sharpe, managed to mimic and enhance the natural process that a tooth undergoes when it is damaged – the mobilisation of stem cells.

“The Wnt signalling pathway is activated, the stem cells are switched on and they then make specific cells that can carry out the repair,” Sharpe explains. “This happens naturally for small repairs, but not for big stuff. For example, when a dentist comes along, removes the decay in your tooth and makes a big hole, it can’t repair itself. What we argued is that if we can enhance this by putting this drug in, the tooth may be able to repair these big holes. And that’s what we’ve done.”

"Whenever you put cement into anything you’re gluing it in, so it can come out or develop cracks, fissures or leaks."

In an animal model, the process the researchers have developed was so effective that, within a few weeks, the tissue that carries out the repair, dentine, had completely regenerated. “This process would normally fail because the hole is too big, but by enhancing the process we’ve made it so that it can repair that big hole,” Sharpe says.

He believes this will work much better than the current standard of treatment – fillings. “Whenever you put cement into anything you’re gluing it in, so it can come out or develop cracks, fissures or leaks,” he explains. “Our method is a continuous repair, so there’s no potential to develop those kinds of things. It would be a much more substantial treatment and because of that, there should be fewer visits to the dentist required.”

The challenges, of course, are to make the treatment as simple as putting cement into a tooth, which Sharpe says it already is, and cost comparative. “We don’t quite know that yet,” he admits. “But because it’s a small molecule drug, it should be quite cheap.”

Next steps

After testing in animal models, the next step for a new treatment would usually be a Phase I clinical trial to work out whether the drug is safe for humans. However, as tideglusib has already been through this stage, when it was being trialled as an Alzheimer’s drug, the team should be able to skip straight to Phase II. “This would save a huge amount of money and a huge amount of time,” Sharpe notes. “If we can get approval from the authorities, we could actually then do a study that is directly in patients, looking at the efficacy of the drug.”

If all goes to plan, the aim is to be in a position to secure funding to start Phase II trials in about a year. These would then run over approximately a two-year period. “You’ve got to collect the right kinds of patients, find the patients that want to be in the trial, then you’ve got to have a period when you follow them,” Sharpe explains. “For example, if we wanted to have 200 patients, you can’t treat all of those in the first week, you’ve got to stagger them. We’d need a good two years for the trial.”

Dentistry – the low hanging fruit

Regenerative medicine, which falls more or less into two camps (growing cells and putting them into a patient or giving something to the patient that stimulates their own cells to repair themselves), is being explored for all sorts of applications all over the world, from cancer to muscle disease. Unusually, though, it may be dentistry that is one of the first big beneficiaries of the field, according to Sharpe.

“Dentistry is usually decades behind everything else I’m afraid,” he says. “But in this case it’s the low hanging fruit. In America in particular, there is a lot of effort being placed on using these same kinds of techniques to enhance bone and cartilage repair but teeth are a bit easier because they’re accessible, you don’t need surgery to get to them and if something goes wrong, it’s very easy to correct it.”

Add to this millions of potential patients that could benefit from the technology, and it’s little wonder that dentistry is leading the way in this area. “I think it just provides an example, of which there are very few, where stem cell biology can have a major impact on something very, very simple,” Sharpe concludes.