An article in the journal Neuropsychopharmacology reports that Anavex Life Sciences Corporation’s ANAVEX 2-73 dose-dependently blocks Tau and amyloid-beta proteins and memory deficit in a mouse model of Alzheimer’s disease (AD). A reduction in these two main hallmarks of Alzheimer’s may have the potential to stop, slow, or reverse the disease. The report also suggests that, because it is targeting the mixed muscarinic and Sigma-1 receptors, ANAVEX 2-73 is able to achieve its effect further “upstream” in the AD cascade. This compares, Anavex spokespersons note, to most other current AD clinical development compounds that are mainly downstream and single-targeted approaches, which might be limited by adverse effects. They also point to the fact that the mixed muscarinic and Sigma-1 agonist ANAVEX 2-73 exhibited powerful effects despite its moderate affinity for these receptors, emphasizing its great advantage for potential therapy in AD.
Tangui Maurice, PhD, one of the study authors, says, “ANAVEX 2-73 also dose-dependently reduced C99 levels in the hippocampus, an effect which researchers are currently trying to achieve with BACE inhibitors. In the mouse model we also confirmed the central role of the kinase GSK-3 beta in Alzheimer’s disease toxicity through drugs acting either directly as GSK-3 beta inhibitors, or indirectly as mixed muscarinic and Sigma-1 ligands. Both can efficiently alleviate these two major alterations observed in the Alzheimer’s animal model as well as in Alzheimer’s patient brains. However, by targeting GSK-3 beta indirectly as ANAVEX 2-73 does through muscarinic and Sigma-1 ligands, we could avoid the toxicity seen by directly targeting GSK-3 beta,” Read the study.
