Suvorexant Cuts Tau Phosphorylation and Amyloid-β Concentrations

Proof-of-concept study is ‘encouraging’ for repurposing insomnia drug, authors say

By Lori Solomon HealthDay Reporter

FRIDAY, April 28, 2023 (HealthDay News) — The insomnia drug suvorexant acutely decreases tau phosphorylation and amyloid-β concentrations in the central nervous system, according to a study published online April 20 in the Annals of Neurology.

Brendan P. Lucey, M.D., from the Washington University School of Medicine in St. Louis, and colleagues evaluated the acute effect of suvorexant, a dual orexin receptor antagonist, on amyloid-β, tau, and phospho-tau. The analysis included 38 cognitively unimpaired participants (45 to 65 years) who were randomly assigned to placebo (13 adults), suvorexant 10 mg (13 adults), or suvorexant 20 mg (12 adults).

The researchers found that the ratio of phosphorylated-tau-threonine-181 to unphosphorylated-tau-threonine-181 decreased 10 to 15 percent in participants treated with suvorexant 20 mg versus placebo. However, there were no decreases seen in phosphorylation at tau-serine-202 and tau-threonine-217 with suvorexant. Compared with placebo, suvorexant decreased amyloid-β 10 to 20 percent starting five hours after drug administration.

“We don’t yet know whether long-term use is effective in staving off cognitive decline, and if it is, at what dose and for whom. Still, these results are very encouraging,” Lucey said in a statement. “This drug is already available and proven safe, and now we have evidence that it affects the levels of proteins that are critical for driving Alzheimer’s disease.”

Several authors disclosed financial ties to C2N Diagnostics and/or Merck; Merck is the manufacturer of suvorexant.

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