[LUM#10] Alzheimer's: slowing down memory loss
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. This is a strange protein to which neuropharmacologist Tangui Maurice has devoted nearly 30 years of research.
This is a new hope for Alzheimer's patients. A progressive neurodegenerative disease whose warning signs "are often cognitive, " explains Tangui Maurice, a researcher at the Molecular Mechanisms in Neurodegenerative Dementias (MMDN) laboratory. "These include memory problems, spatial and temporal disorientation, and deregulation of the response to stress or novelty."
Neuroprotective power
It was in the 1990s that the biologist discovered the anti-amnesic power of certain molecules capable of activating Sigma-1, a protein that had previously been incorrectly classified as an opioid receptor. In 1995, he developed a pharmacological model that induced Alzheimer's symptoms in rats within a week, allowing him to test the role of Sigma-1 in the disease.
Tangui Maurice then understood the unique nature of Sigma: "It is not a conventional receptor; rather, its role is to modulate other proteins to enable them to exert their effect." Working with the American company Anavex, he tested original molecules, demonstrating that they are neuroprotective and that their effect is amplified by Sigma-1.
Impressive results
The researchers then developed a molecule called ANAVEX2-73, which proved effective in mice before being tested on around 30 patients. "Two cognitive scores were observed. On the one hand, an autonomy score: do you still live at home, do you do the dishes, do you go to bed on your own?" The results were good and even equivalent to those of donepezil, a drug currently prescribed to patients.
The second score relates to memory quality. "We see a loss limited to 1 point in three years, whereas untreated patients lose 6 points. That's impressive," notes the researcher. These scores have enabled ANAVEX2-73 to move to the next stage and is currently being tested on 450 patients. The results should be known within three years and, if successful, it is very likely to be brought to market.
First-in-class
This research is promising, especially since ANAVEX2-73 is only the first Sigma-1 molecule to be developed, points out Tangui Maurice: "It's 'first-in-class,' but it may not be the best. We are continuing to search for other, more selective molecules. " This treatment does not lead to a cure, but it could be a powerful ally in slowing down Alzheimer's. "The disease starts at 70 or 80 years of age, so if we can stabilize patients for 10 years, that's a huge gain for them and their loved ones. The neuroprotective strategy really makes sense," concludes the researcher.
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