A new drug engineered to address the root cause of narcolepsy type 1 (NT1) doesn’t just curb the hallmark symptoms, such as overwhelming sleepiness and sudden muscle weakness. New research suggests that it also appears to boost memory, improve attention span, and helps sharpen executive functioning.
According to a new secondary analysis of a phase 2 randomized clinical trial, the experimental medication oveporexton refined several crucial cognitive abilities in adults living with NT1.
The results, published in JAMA Neurology, suggest that targeting orexin receptor 2 (OX2R) might address one of the most neglected aspects of NT1: the cognitive fog that persists even after sleepiness improves.
A Drug That Might Help Clear the Mind
Research shows that NT1 emerges when neurons in the hypothalamus that produce orexin taper off. It’s a development that disrupts the brain’s normal regulation of sleep, muscle tone, attention, arousal, and reward processing. For years, clinicians have targeted excessive daytime sleepiness and cataplexy for treatment.
But patients repeatedly complain of an altogether different burden. They struggle to think clearly, learn new things, concentrate, and remember details. Multiple surveys report that up to 90% of adults with NT1 describe notably cognitive difficulties, even if they’re already receiving treatment.
Oveporexton, developed by Takeda Pharmaceuticals, is part of a new class of selective orexin receptor 2 agonists designed to directly replace lost signaling instead of compensate for it.
An earlier analysis of the same clinical trial showed robust improvements in sleepiness, cataplexy, and quality of life. But this follow-up study sought to explore new territory. Would restoring orexin signaling also improve thinking?
Inside the Trial
The international team of researchers analyzed 112 adults between the ages of 18 and 70 who received either placebo or various dose regimens of oveporexton over eight weeks. Participants stopped all narcolepsy medications before the trial and researchers tested them one hour after their morning dose. The study’s authors also scored cognition using multiple neuropsychological measures.After eight weeks, the participants on oveporexton showed dramatic improvement on all four measures across nearly every dose – compared to those taking the placebo. For attention, placebo patients actually slowed over time, while treated patients improved. For memory, oveporexton users made far fewer errors, with medium-to-large effects across doses. Executive functions also improved, especially at higher doses.
Notably, researchers also logged improvements both one and seven hours after dosing, suggesting cognitive benefits that persisted throughout the day.
Why a Sleep Drug Affects Thinking
The researchers argue that these results back a broader biological theory: that orexin signaling is about more than just wakefulness. It seems to support areas of the brain responsible for attention, memory, motivation, and decision-making.
Other evidence supports this link. In rodents, damage to these orexin-targeted regions hampers learning and working memory. At the same time, drugs that block orexin receptors (such as insomnia meds) can cause notable cognitive slowing – even in healthy adults.
By selectively activating OX2R, oveporexton might be reactivating a network of cognition-supporting neurons that has been offline since disease onset.
What Comes Next?
While certainly promising, the study doesn’t come without its share of caveats.
- The trial population was mostly white.
- The researchers also note that they can’t yet determine whether cognitive improvements are a direct effect on neural networks or whether it’s a secondary effect of better wakefulness.
Still, the findings mark a meaningful shift in narcolepsy research. For the first time, a medication aimed at the biology of orexin deficiency shows ties to improvements in how patients think and sleep.
Further Reading
Narcolepsy and Orthostatic Intolerance in an Adult With Ehlers-Danlos Syndrome
