Abstract
Tideglusib®, a GSK-3 inhibitor, was initially tested for the treatment of Alzheimer’s disease. However, a recent report has suggested its potential off-label use for the treatment of dental cavities. Even if this effect is not yet confirmed, this off-label use can have significant public/dental health consequences, mainly because of the large number of patients with cavities. The purpose of this mini-review is to perform an ethical analysis of the use of Tideglusib in dentistry. The ethical analysis identified three main areas in which ethical breaches could be significant: 1) respect for the autonomy of the patient, 2) issues raised by horizontal shifts in the translational research process, and 3) the conflict between dental beneficence and general non-maleficence. In conclusion, the use of Tideglusib in dentistry should respect the same strict ethical and regulatory criteria from clinical medicine. A translation of the potential risks should be done only after large-scale, phase-III/IV clinical trials, explicitly designed to test the usefulness of this drug in dental medicine.
Highlights
Serine/threonine kinase glycogen synthase kinase-3 (GSK-3) is an essential human kinase, which is able to interact with more than 100 known substrates (Beurel et al, 2015) [see Figure 1 detailing the mechanisms of activation/inhibition (Llorens-Marítin et al, 2014)]
In a phase-IIa clinical trial, the treatment was discontinued in 35% of all the active subjects, mainly due to adverse reactions
Sato et al showed that GSK-3 inhibition through 6-bromoindirubin-3′-oxime activates the Wnt pathway, maintains an undifferentiated phenotype of embryonic stem cells, and retains the pluripotent state-specific transcription factors Rex-1, Oct-3/4, and Nanog (Sato et al, 2004)
Summary
Serine/threonine kinase glycogen synthase kinase-3 (GSK-3) is an essential human kinase, which is able to interact with more than 100 known substrates (Beurel et al, 2015) [see Figure 1 detailing the mechanisms of activation/inhibition (Llorens-Marítin et al, 2014)]. Sato et al showed that GSK-3 inhibition through 6-bromoindirubin-3′-oxime activates the Wnt pathway, maintains an undifferentiated phenotype of embryonic stem cells, and retains the pluripotent state-specific transcription factors Rex-1, Oct-3/4, and Nanog (Sato et al, 2004). Based on this effect, a recent study by Neves et al evaluated the potential for natural tooth repair by using small molecule GSK-3 antagonists, such as Tideglusib. Before potentially using such therapies for dental cavities, a closer look should be taken at some of the main ethical issues posed by the use of this drug, and the main potential problems arising from their indiscriminate usage should be emphasized
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