Insomnia is a common sleep disorder that affects millions of people worldwide and can lead to a range of negative health consequences. While there are many treatments available for insomnia, researchers have recently discovered a potential new use for a class of drugs called dual orexin receptor antagonists (DORAs). These drugs block the activity of a chemical in the brain called orexin, which is responsible for promoting wakefulness.
By reducing orexin activity, DORAs help people fall asleep and stay asleep. However, recent studies have suggested that these drugs may also have the potential to lower levels of proteins linked to Alzheimer’s disease.
New research published in National Institutes of Health says Alzheimer’s is a debilitating neurodegenerative disease characterized by the build-up of proteins called amyloid-β and tau in and around neurons in the brain, leading to their death. As more than six million people in the U.S. are thought to be living with Alzheimer’s disease, researchers have been working tirelessly to develop treatments that can slow, stop, or even reverse the damage seen in the disease.
Recently, researchers have discovered that a class of drugs called dual orexin receptor antagonists (DORAs) has been developed to treat insomnia by blocking orexin, a chemical in the brain that promotes wakefulness. In mice, blocking orexin with a DORA reduced levels of amyloid-β in the brain. To investigate whether this could translate to humans, NIH-funded researchers led by Dr. Brendan Lucey from Washington University in St. Louis recruited 38 volunteers into a small, proof-of-concept study.
All participants were between the ages of 45 to 65 and cognitively healthy. The researchers randomly assigned them to receive either two higher doses of a DORA called suvorexant over 36 hours, two lower doses of suvorexant, or a placebo. The team then measured changes in levels of amyloid-β and a form of tau called phosphorylated tau in the cerebrospinal fluid.
The study found that people receiving suvorexant did not show an increase in sleep time or quality over the night of the study. However, those who received the higher dose of the drug showed a 10-15% drop in phosphorylation at a site on tau that contributes to tau tangles. Additionally, by twelve hours after receiving high-dose suvorexant, participants had amyloid-β levels 10-20% lower than those in the placebo group.
Although the study’s results are encouraging, the researchers cautioned that they don’t yet know whether long-term use of suvorexant is effective in staving off cognitive decline and if it is, at what dose and for whom. The researchers are now launching a clinical trial to study the longer-term effects of orexin inhibition on people who are at risk for developing dementia.
Despite the need for further research, the study’s findings offer hope that a treatment for Alzheimer’s disease may be on the horizon. As suvorexant is already available and proven safe, the researchers believe that their findings could lead to the development of a new treatment for Alzheimer’s disease.
