Suvorexant acutely effective in reducing Alzheimer’s-related biomarkers

Key takeaways:

• Researchers aimed to assess suvorexant as amyloid arresting treatment in midlife adults with sleep issues.
• Treatment with suvorexant 20 mg led to acutely decreased levels in several Alzheimer’s-related biomarkers.

PHILADELPHIA — In cognitively healthy but sleep-poor adults in midlife, treatment with 20 mg suvorexin led to acute decreases in Alzheimer’s-related biomarkers compared with 10 mg of the drug and placebo, according to a presenter.

“Soluble levels of amyloid beta increase and decrease with sleep-wake activity in humans,” Brendan P. Lucey, MD, MSCI, FAASM, professor and section chief, section of sleep medicine in the department of neurology at Washington University School of Medicine in St. Louis, stated during his presentation. “Which raises the question of ‘can you manipulate sleep to manipulate the levels of these proteins?’”

Because prior research established that accumulated sleep loss increases amyloid-beta and tau protein biomarkers indicative of Alzheimer’s-related pathology, Lucey and colleagues sought to determine whether suvorexant — a dual orexin receptor agonist and one of only three FDA-approved drugs to address insomnia — could impact amyloid beta production in adults aged between 45 and 65 years who are cognitively normal but have sleep disorders.

Their translational study included 39 individuals given either 10 mg (n = 13; mean age, 56.95 years), 20 mg suvorexant (n = 12; mean age, 54.3 years) or placebo (n = 13; mean age, 55.94 years).

All participants arrived at a research unit within the university at 8 p.m. and were fitted with a catheter placed on their back, then an hour later received either suvorexant or placebo with cerebrospinal fluid (CSF) collection for biomarker sampling occurring every 2 hours through the night until 8 a.m. the following day. Participants returned to the same location at 8 p.m., and the process was repeated that evening through 8 a.m. the following day.

According to results, those in the 20 mg suvorexant treatment group registered acutely decreased levels of CSF amyloid beta (A-beta 38/40/42), whereas those given 10 mg suvorexant had a much more consistent change in amyloid beta levels, compared with placebo.

Similarly, the researchers observed that 20 mg suvorexant registered an acute decrease in CSF phosphorylated tau-181, along with a moderate decrease in phosphorylated-tau 217 compared with 10 mg suvorexant or placebo.

Lucey additionally posited that future studies may assess whether 10 mg or 20 mg lemborexant may have a significant effect on CSF p-Tau proteins.

“We’re looking at giving drugs like suvorexant for longer periods of time and looking at how these markers change, over hours if not ... over months,” Lucey noted. “There could be important mechanistic differences in these drugs that need to be tested more thoroughly.”