Anavex Highlights Role of Sigma-1 Brain Receptor in Alzheimer’s Development

Anavex Life Sciences has published a study demonstrating the sigma-1 receptor’s role in Alzheimer’s disease. The data contained in it supports the New York-based company’s development of compounds stimulating this receptor as a way of treating the illness.

The study, “Sigma-1 Receptor Agonists Induce Oxidative Stress in Mitochondria and Enhance Complex I Activity in Physiological Condition but Protect Against Pathological Oxidative Stress,” appeared in the journal Neurotoxicity Research. It showed that sigma-1 boosting compounds act as antioxidants and protect energy-making structures called mitochondria in conditions such as Alzheimer’s.

Meanwhile, another study, “Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the σ1 receptor,” published in the journal Behavioural Brain Research, showed that a lack of sigma-1 worsens toxicity brought on by amyloid proteins.

“Both findings are consistent with the concept that sigma-1 receptor activity seems to be essential for cell survival under stress, with the ability to counter the different manifestations of Alzheimer’s disease and other neurodegenerative pathologies,” Dr. Tangui Maurice, senior author of both studies and a professor at the French scientific research institute INSERM, said in a press release.

Researchers believe that abnormal mitochondrial processes and linked oxidative damage are key to driving disease in several neurodegenerative conditions. People with Alzheimer’s show signs of oxidative damage long before they have substantial amyloid plaques, which are considered a telltale sign of the disease.

The Neurotoxicity Research article provided insights into the mechanisms of action of three Anavex compounds developed for the treatment of Alzheimer’s and other neurodegenerative conditions. It suggests that all three may act as potent neuroprotectors in people with the disease.

The second publication indicated that if these neuroprotective effects are missing, amyloid accumulation worsened learning and memory problems, as well as other markers of disease, in mice models of Alzheimer’s.

“These results seem to further validate sigma-1 receptor agonism as a therapeutic target for the treatment of neurodegenerative diseases,” said Dr. Christopher U. Missling, president and CEO of Anavex.

One of Anavex’s compounds, Anavex 2-73, is in clinical development for Alzheimer’s, and the company recently announced it will soon launch a Phase 2/3 trial of the drug candidate.

Early data from the extension of the Phase 2a study of the compound indicated that people in the highest dose-group actually improved with the treatment, raising hopes that Anavex 2-73 may break the negative trend of failures in Alzheimer’s drug development.