Alzheimer's: slowing down the process of forgetting

Effectively stabilizing the progression of Alzheimer's disease could become possible thanks to the discovery of the neuroprotective and anti-amnesic effects induced by Sigma-1. A strange protein to which neuropharmacologist Tangui Maurice has devoted almost 30 years of research.

A new hope for Alzheimer's patients. A progressive neurodegenerative disease whose warning signs "are often cognitive", explains Tangui Maurice, researcher at the Molecular Mechanisms in Neurodegenerative Dementia (MMDN) laboratory. "These are problems with memory, spatial and temporal disorientation, and deregulation of response to stress or novelty.

Neuroprotective power

It was in the 90s that the biologist discovered the anti-amnesia power of certain molecules capable of activating Sigma-1. Until then, this protein had been incorrectly classified as an opiate receptor. In 1995, he developed a pharmacological model that induced Alzheimer's symptoms in rats within a week, enabling him to test Sigma-1's role in the disease.

Tangui Maurice then understood the particular nature of Sigma: "It's not a classic receptor, but rather its role is to modulate other proteins to enable them to have their effect". With the American company Anavex, he tested original molecules, showed that they were neuroprotective, and that the effect was amplified by Sigma-1.

Impressive results

The researchers then developed a molecule called ANAVEX2-73, which proved its worth in mice before being tested on some thirty patients. "Two cognitive scores were observed. One was an autonomy score: do you still live at home, do you do the dishes, do you go to bed by yourself?" The results were good, and even equivalent to those of donepezil, a drug currently prescribed to patients.

The second score concerns memory quality. "We see a loss limited to 1 point over three years, whereas untreated patients lose 6 points. This is impressive," notes the researcher. These scores have enabled ANAVEX2-73 to be taken to the next level, and is currently being tested on 450 patients. Results should be available within three years, and if successful, the product will probably be marketed.

"First-in-class

This promising research is all the more important given that ANAVEX2-73 is only the first Sigma-1 molecule to have been developed, as Tangui Maurice points out: "It's the first-in-class, but it may well not be the best. We're continuing our search for other, more selective molecules. A treatment which does not open the way to a cure, but which could be a powerful ally in slowing Alzheimer's. "The disease starts at the age of 70 or 80, and if we can stabilize patients for 10 years, that's a huge gain for them and their families. The neuroprotective strategy really makes sense," concludes the researcher.