Tideglusib

There are few classes of GSK-inhibitors, including lithium (Martinez et al., 2011), the small peptide L803mts10, and members of the thiazolidinedione family, containing non-competitive inhibitors of GSK-3, such as TDZD-8 (Shapira et al., 2007) or Tideglusib® (Noscira, Madrid, and Spain), the latter having an irreversible inhibitory effect on GSK-3 (del Ser et al., 2013). The inhibition of the GSK-3 pathways through distinct mechanisms has been associated with a wide range of adverse reactions, ranging from mild, such as vertigo—or diarrhea (del Ser et al., 2013)—to very severe, such as hypoglycemia—or tumorigenesis (Martinez et al., 2011). The use of Tideglusib specifically was associated with mild-moderate adverse reactions, which included transient increases in serum creatine kinase, ALT—or gGT—diarrhea, nausea, cough, fatigue, and headache (del Ser et al., 2013). In a phase-IIa clinical trial, the treatment was discontinued in 35% of all the active subjects, mainly due to adverse reactions (del Ser et al., 2013).

Tideglusib is under investigation for multiple applications:

• Alzheimer's disease and progressive supranuclear palsy. As of 2017 it was undergoing Phase IIa[2] and IIb clinical trials.[3][4][5][6] The first trial to be published (in English) was Phase II and demonstrated that tideglusib was well tolerated, except for some moderate, asymptomatic, fully reversible increases in liver enzymes.[4]
• Tooth repair mechanisms that promotes dentine reinforcement of a sponge structure until the sponge biodegrades, leaving a solid dentine structure. In 2016, the results of animal studies were reported in which 0.14 mm holes in mouse teeth were permanently filled.[7][8]
• Tideglusib is being studied in Phase II clinical trials as a treatment for congenital/juvenile-onset myotonic muscular dystrophy type I.[9]