Compounds that Target Sigma-1 Receptor Offer Promise in Battling Alzheimer’s, Says Anavex
New York-based Anavex Life Sciences presented data at the recent 13th International Conference on Alzheimer’s & Parkinson’s Diseases in Vienna showing that its compounds binding to the sigma-1 receptor hold promise in treating Alzheimer’s disease.
Besides the well-known accumulation of amyloid beta peptide and the formation of senile plaques, researchers have extensively described the brain inflammation and reduced synaptogenesis (the formation of new synapses between neurons) in Alzheimer’s.
Furthermore, evidence suggests that mitochondria dysfunction precedes the onset of pathological hallmarks in Alzheimer’s. The sigma-1 receptor — highly expressed in the central nervous system — resides in the mitochondria. In pre-clinical studies, its activation by ligands stimulated neuroprotection and normalized mitochondria function. However, sigma-1’s effects on mitochondria in pathological conditions related to Alzheimer’s are still unknown.
McGill University’s Hélène Hall, PhD, delivered the first poster presentation, “Targeting M1 muscarinic and sigma-1 receptors in Alzheimer’s disease: Reversal of pathological hallmarks and associated cognitive dysfunction in McGill-R-Thy1-APP rats.” This study showed that, using transgenic mice with Alzheimer’s-like amyloid pathology, compound Anavex 3-71 (five months of daily treatment), reduced inflammatory response in the brain and increased synaptogenesis. Furthermore, the compound decreased amyloid pathology and fully reversed Alzheimer’s-related cognitive deficits.
Of note, the mice were 13 months old at the start of the study, an age when Alzheimer’s-related symptoms are fully developed in this disease model. Importantly, researchers observed the benefits of Anavex 3-71 following a month-long drug washout (elimination from the body), which further supports this drug’s therapeutic potential.
The second poster presentation, “The dual regulation of oxidative stress by SIGMA1 receptors in physiological or pathological conditions,” was led by Tangui Maurice, PhD, director of research at INSERM, Université de Montpellier, in France. It showed that Anavex 2-73, Anavex 3-71 and Anavex 1-41 reduced oxidative stress and ameliorated mitochondria function after application of amyloid beta.
“These new results provide converging evidence on mechanism of action as well as possible disease-modifying properties potentially by restoring homeostasis by means of the sigma-1 receptor agonists in our pipeline,” Anavex CEO Christopher U. Missling, PhD, said in a press release. “This data also provides a foundation for our ongoing translational research efforts.”