Starting point
A very early phenomenon during Alzheimer's disease is the duplication of DNA in the affected neurons, which become tetraploid.
Tetraploidy is associated with an increase in cell size that can affect neuronal physiology, resulting in functional alterations in the brain.
Initial research
The research conducted by Tetraneuron has verified that DNA duplication in neurons depends on a molecule called E2F4, known for its ability to regulate the cell cycle. The role of E2F4 as an inducer of neuronal tetraploidy depends on its phosphorylation by the p38MAPK kinase
Essential conclusion
The use of a dominant negative form of E2F4 incapable of being phosphorylated by p38MAPK (E2F4-DN) prevents neuronal tetraploidy and results in cognitive improvements in murine Alzheimer models.
This strategy could be used as a therapy to block the progression of Alzheimer's disease.
Timeline
2012 Identification of Therapeutic Target
Discovery phase
2015 Validation of the Therapeutic Target
2016 Identification of the Leading Compound
2017 Validation of the Leading Compound
Validation phase
Optimization of the blocking compound of neuronal tetraploidization E2F4-DNEvaluation phase
Neural tetraploid assessment and cognitive ability in murine models of Alzheimer's treated with E2F4-DNStudies
Confirmation studies2018 Pre-clinical Phase
‣ Tests with living organisms and formulation of the drug
‣ Tests on living organisms and on cells or tissues
‣ Formulation of the drug for use in medical tests
‣ Pharmacology and toxicology studies2019 Clinical phase
‣ Previous research and drug testing in patients
‣ Regulatory approval