[LUM#10] Alzheimer's: Slowing Down Memory Loss
Effectively slowing the progression of Alzheimer’s disease may soon become possible thanks to the discovery of the neuroprotective and anti-amnesic effects of Sigma-1, a unique protein to which neuropharmacologist Tangui Maurice has devoted nearly 30 years of research.
This offers new hope for patients with Alzheimer’s disease. A progressive neurodegenerative disorder 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 dysregulation of the response to stress or novelty.”
Neuroprotective properties
It was in the 1990s that the biologist discovered the anti-amnesic properties of certain molecules capable of activating Sigma-1—a protein that had previously been mistakenly 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 came to understand Sigma’s unique nature: “It’s not a conventional receptor; rather, its role is to modulate other proteins so they can exert their effects.” Together with the American company Anavex, he tested novel molecules, demonstrating that they have neuroprotective effects and that these effects are amplified by Sigma-1.
Impressive results
The researchers then developed a molecule called ANAVEX2-73, which had proven effective in mice before being tested on about thirty patients. “Two cognitive scores were assessed. First, an independence score: do you still live at home, do you wash the dishes, do you get into bed on your own?” The results are good and even comparable to those of donepezil, a medication currently prescribed to patients.
The second score pertains to memory function. “We see a loss limited to just 1 point over three years, whereas untreated patients lose 6 points. That’s impressive,” notes the researcher. These results have allowed ANAVEX2-73 to move to the next phase and is currently being tested on 450 patients. Results are expected within three years, and if successful, the drug 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, as Tangui Maurice points out: “It’s ‘first-in-class,’ but it may very well not be the best. We’re continuing to search for other, more selective molecules. ” A treatment that doesn’t lead to a cure, but could be a powerful ally in slowing down Alzheimer’s. “The disease typically begins at age 70 or 80; if we can stabilize patients for 10 years, that’s a huge benefit for them and their loved ones. The neuroprotective strategy really makes sense,” concludes the researcher.
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