Up until now, the team had only tested and evaluated injected epothilone D, a brain-penetrant MT-stabilizer, in mice and AD patients. However, in spite of the fact that epothilone D is recognized as a potential treatment for Alzheimer’s and cancers, the compound has been limited in use, as the injectable form brings with it a great deal of pain for the patient,
Carlo Ballatore, Kurt Brunden and colleagues wanted to test new compounds already identified as potential anti-fungal and anti-cancer therapies “from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function,” they wrote.
According to the information provided, the results, published on the ACS’s Journal of Medicinal Chemistry, appear to have confirmed that representative compounds from these series increased MT-stabilization in the brains of wild-type mice, leading scientists to believe that they could be viable oral therapies for treating Alzheimer’s Disease.
Microtubules are cellular components made of protein that reside inside cells, critical for performing cell growth and division and for transporting nutrients. In a healthy brain, the protein known as tau stabilizes them. However, in Alzheimer’s brains, tau doesn’t bind well to microtubules and forms a brain mass.
Scientists believe that this disorder is responsible for Alzheimer’s symptoms, such as memory loss, dementia, and nerve cell death.
This has led to Ballatore’s team claiming that “Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer’s disease.” Alzheimer’s affects more than 5 million Americans.