Tideglusib (NP-12, NP031112) is a potent and irreversible[1] small molecule glycogen synthase kinase 3 (GSK-3) inhibitor.
Other GSK inhibitors[edit]
There are few classes of GSK-inhibitors, including lithium (Martinez et al., 2011), the small peptide L803mts10, and members of the thiazolidinedione family, containing 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 (Dominguez et al., 2012). 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, due to such adverse effects (del Ser et al., 2013).
Tideglusib and colagen are both materials used for tooth regeneration. Colagen's function is more of a bone matrix or a carrier to make dentine to grow on. Tideglusib function is to stimulate (a kind of signaling) growth of the dentin. If I am correct in understanding its research content, these materials are dissolved upon regeneration process. Colagen is soaked in tideglusib and it is placed inside hole of the tooth. I believe that hole must expose the pulp. I am not familiar at what stage the pulp (dead or alive) has to be to make it work. Then the top of the filled hole has to be covered with filling like biodentine or mta. Kolspon Collagen alone, 50 nM Tideglusib dissolved and diluted in DMSO. The tideglusib use is a chemical approach for regeneration of the tooth. Past research by Robert O. Becker has demonstrated that regeneration is not confined to the bone but to any other living cells and tissues and not necessarily by chemical approach but by electrical polarization. According to his research, the bone (and the tooth) has similar properties of a piezo crystal.
At the moment of the removal of the root, the remnant of the pulp is torn but it is not cauterized so we say is still alive.By introducing colagen and tricalcium phosphate plus a minimal amount of tideglusib the live tissue will absorb the biomaterials and initiate a reaction of adherence ( hopefully) that will continue with the formation of new tissues in the next 3 months. If we add periodontal cells to the scaffold, we should also regenerate the membrane which will be needed later when we build the prosthesis. Electric polarization had been tried in rodents, but unfortunately our patients are not mice or rabbits, so using the Helsinky protocol we should be able to try the procedures in humans.
Joe Orti , From other non-dental clinical trials, about 500-1000mg of Tideglusib were delivered to humans for 26 weeks. Probably the above mentioned symptoms occurs from these trials. The dental trial in mouse on other hand, the dosage was 21 pg with sponges which is human equivalent of 63 ng. This is far below threshold dosage of the human trials mentioned above.
In experimental trials cavities are cleaned. However, in real life street dental office, do cavities need to be cleaned or can nature do the dirty work?
Joe Orti , it sounds like the tooth does not have an ability to eliminate the damage even when it is assisted with Tideglusib. What about silver diamine fluoride (SDF) or Calcium Hydroxide without drilling? When observing x-rays and images of experimental results in clinical trials of Tideglusib, the cavities were mechanically induced and they were usually small. Most teeth in patients have large cavities, sometimes half tooth missing due excessive mechanical drilling or trauma. In that case, liquid form of medication will not suffice even when it is colagen impregnated. Therefore 3D printing of bone graft ( solid colagen ? )will be needed for teeth like scissors or canine as a bone-tooth graft. I observed that mechanical drilling does more damage to tooth than cavity itself when regenerating bone is a hard thing to do.
- Badges
- Science topic
- Similar topics
- Mathematics
- Statistics
- Applied Statistics
- Survey Design
- Questionnaire