Alzheimer’s disease and Wilson’s disease

There is currently no effective medication for Alzheimer’s disease. This neurodegenerative disease is characterised by a loss of endogenous copper regulation, which accumulates in amyloid plaques in the brains of patients (six times more than in healthy brains). This phenomenon is responsible for the overproduction of hydroxyl radicals (ROS) which induce neuronal death and, consequently, the loss of cognitive functions. We have synthesised a series of molecules containing an 8-aminoquinoline motif and a diamine side chain (called TDMQ), capable of specifically chelating Cu(II) in a square planar environment. These drug candidates effectively inhibit episodic memory loss in a mouse model mimicking the early stages of Alzheimer’s disease.

A compound in this family, TDMQ20, is also active against Wilson’s disease, a genetic disorder characterised by a toxic accumulation of copper in the liver. In mice, TDMQ20 is more effective than the drugs currently used clinically or in development, in reducing the hepatic load of copper and facilitating its biliary excretion. Unlike reference products, TDMQ20 is not acutely or chronically toxic in mice.Un composé de cette famille, la TDMQ20 est également actif contre la maladie de Wilson, pathologie génétique caractérisée par une accumulation toxique de cuivre dans le foie. Chez la souris, la TDMQ20 est plus efficace que les médicaments actuellement utilisés en clinique ou en développement, pour diminuer la charge hépatique de cuivre et faciliter son excrétion biliaire. Contrairement aux produits de référence, la TDMQ20 ne présente aucune toxicité aigüe ou chronique chez la souris.