Could an FDA-approved sleeping pill reduce abnormal tau and amyloid-beta proteins, and slow Mild Cognitive Impairment (MCI) or dementia, the way Leqembi ™ and Aduhelm ™ are supposed to work?
Researchers at Washington Univ (St. Louis) did an exploratory study of the sleeping pill suvorexant /Belsomra ™ in humans. It was based on results in Alzheimer (AD) mouse model studies that seemed to show that it reduces tau and amyloid proteins.
They divided 38 human volunteer subjects into three groups: one placebo, and two different suvorexant doses, ~13 in each group. “Biomarkers” is a term used in the AD clinical literature, commonly for images of tau or amyloid brain burden as detected by PET scans. This study looked at direct biomarker protein measurements in subjects’ cerebrospinal fluid.
That’s right, these great volunteers, age 45-65, cognitively unimpaired, the majority being white women, all with sleep efficiency issues, had spinal taps…with spinal catheters left in for serial cerebrospinal fluid (CSF) sampling every two hours for 36 hours!
So whatever effect this sleeping pill might have had, it would be on “normal” tau and amyloid beta protein processing in asymptomatic subjects. Because the graphs of results are data dense, we’ll skip those here and just copy the authors’ conclusions:
“Interpretation: In this study, suvorexant acutely decreased tau phosphorylation and amyloid-β concentrations in the central nervous system….”
Tau with phosporylation (one of the subtypes they measured and thought to be activated) was decreased ~10-15%, whereas amyloid beta was reduced ~ 10-20%. [The subjects didn’t sleep better with this pill, but c’mon, who can sleep well with a little tube stuck in your spine, and someone around every two hours to collect 6 mL of your precious bodily fluid behind your back?]
There were no cognitive measures, since that wasn’t really the aim of the study.
For perspective, the anti-amyloid monoclonals Leqembi ™ and Aduhelm ™ seem to significantly decrease brain amyloid, as measured by PET scan. However the quantitation afforded by PET scan interpretation (SUV ratios) may not be as precise or clinically correlate well with the CSF measurements of these proteins. And the clinical impact or meaningfulness of the monoclonals’ results is still a bit controversial.
This was only a small and short term study. Maybe the sleeping pill isn’t as good for the total burden in that time frame, but maybe it could be used over years to decrease accumulation, as the researchers are speculating. The good news is that there are other agents in that class of medications to test.
It would be amazing if it’s tolerated, hits the most offending proteins hypothesized to be the core of the pathophysiology in MCI/AD, and could be proven to stave off cognitive problems. That would be the dream, to eliminate the nightmare of bad proteins so everyone could sleep better, all at the same time, right?….nighty night!
