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Fixing dental decay with Tideglusib

CAN WE REALLY FIX UP TOOTH DECAY WITH A DROP OF MEDICINE ?

February 28, 2017

Ever wondered, what dentistry will be like in the future? Will the traditional "drill and fill" dentistry disappear? Will dentists and other members of the dental team be replaced by robots? Will we be able replace a broken down tooth with a "custom-grown" tooth?

Stem cells regeneration holds a lot of potential for modern day medicine and dentistry. It's exhilarating just Imagining the possibilities! Yet, the obstacles researchers have to solve before the possibilities translate from research to every day clinical practice are many. Growing our own teeth for dental treatment will take many more years of research and validation yet.

Something that may take a little less time than growing an entire tooth but with equally exciting potentials, is the increased regeneration of a layer of the tooth structure – dentine – for repair of tooth cavity or fractured tooth.

We already use dental materials, such as calcium, calcium-phosphate and calcium silicate-based medicaments(1-3), to stimulate dentine repair at present. However the amount of reparative dentine generated is only very little - adequate as a protective barrier or a “biological seal” to prevent damage to the dental pulp but not enough to repair an entire cavity.

The activation of stem cells via low level laser to stimulate growth factors such as transforming growth factor beta-1 (TGF-B1) for dentine regeneration has also been reported.(4) Again, a potentially good idea but so far, the amount of reparative dentine generated in experimental studies have not been adequate to repair the entire tooth cavity.

In January 2017, King's College London published in Scientific Reports, the possibility of growing new dentine, enough to fill an entire tooth cavity.(5) The process relies on the use of Tideglusib – a GSK inhibiting drug that is being tested for treatment of Alzheimer’s disease.(6)

The new approach currently being tested by King’s College London Dental Institute’s Head of Craniofacial Development and Stem Cell Biology, Prof Paul Sharpe and co-workers, involves placing biodegradable collagen sponge soaked with a low dose of Tideglusib (glycogen synthase kinase (GSK-3) inhbitors) to the tooth cavity.(5,7) The collagen sponge biodegrades over time and new dentine is formed in its place, to the point where the entire cavity is repaired by dentine.(5,7) The mechanism of action appears to be related to Tideglusib’s ability to stimulate the activity of stem cells in the dental pulp via Wnt signalling pathway activation.(5,7)

While the research certainly sounds exciting, it will be some time yet before research translates to clinical practice. The King's College London study was performed using the teeth of mice and cavities that were cut into the teeth deliberately.(5) The regeneration to fill the entire cavity took at least 4 weeks.(5) Human cavities, will pose a bigger challenge in every sense of the word. In addition to a big size difference, human cavities, with all the inflammatory and infective processes going on, will likely affect stem cell responses and add further complications to the challenge. Moreover, Tideglusib is still undergoing clinical trials and safety testing for its intended uses in medicine…so translating its use to dentistry, is unlikely to happen in the near future.(8)

If and when this piece of research finally translates to everyday practice, what an exciting day it will be!

 

REFERENCES

  1. Li Z, Cao L, Fan M, Xu Q. Direct pulp capping with calcium hydroxide or mineral trioxide aggregate: a meta-analysis. J Endod 2015; 41(9): 1412-1417. doi: 10.1016/j.joen.2015.04.012.
  2. Cao Y, Mei ML, Xu J, Lo EC, Li Q, Chu CH. Biomimetic mineralisation of phosphorylated dentine by CPP-ACP. J Dent 2013; 41(9): 818-825. doi: 10.1016/j.dent.2013.06.008
  3. Song M, Yu B, Kim S, Hayashi M, Smith C, Sohn S, Kim E, Lim J, Stevenson RG, Kim RH. Clinical and molecular perspectives of reparative dentin formation. Lessons learned from pulp-capping materials and the emerging roles of calcium. Dent Clin North Am 2017; 61(1): 93-110. doi: 10.1016/j.cden2016.08.008.
  4. Arany PR, Cho A, Hunt TD, Sidhu G, Sin K, Hahm E, Huang GX, Weaver J, Chen A C-H, Padwa BL, Hambin MR, Barcellos-Hoff MH, Kulkarni AB, Mooney DJ. Photoactivation of endogenous latent transforming growth factor-B1 directs dental stem cell differentiation for regeneration. Science Translational Medicine 2014; 6(238): 238-269. DOI: 10.1126/scitransimed.3008234.
  5. Neves VC, Babb R, Chandrasekaran D, Sharpe PT. Promotion of natural tooth repair by small molecule GSK3 antagonists. Sci Rep 2017 Jan 9;7:39654. doi: 10.1038/srep39654.
  6. Alzforum. Tideglusib. Accessed online: http://www.alzforum.org/therapeutics/tideglusib.
  7. King’s College London. News. Natural tooth repair method, using Alzheimer’s drug , could revolutionise dental treatments. Accessed online: http://www.kcl.ac.uk/dentistry/newsevents/news/newsrecords/2017/January/Natural-tooth-repair-method-using-Alzheimer's-drug-could-revolutionise-dental-treatments.aspx.
  8. PubChem. Tideglusib. Drug and Medication Information. Accessed online: https://pubchem.ncbi.nlm.nih.gov/compound/Tideglusib#section=Drug-and-Medication-Information

 

In Oral Health Tags tooth, decay, cavityfree, remineralisation, dentine, enamel, reparative dentine, tooth hard tissue regeneration, stem cells, Tideglusib, GSK3 inhibitors, dental breakthrough, natural tooth repair, dental cavity, dental, dental treatment, Toothbunny
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