ArticleProceedings of the National Academy of Sciences of the United States of America2018
Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Production of Chitosan-PVA Coated Vitamin E and Ephedrine Nanoparticles Using Electrospraying for the Treatment of Narcolepsy.Molecules (Basel, Switzerland) · 2026Article
- Longitudinal Associations of Serum Orexin-A With Physical Activity and Sleep in Schizophrenia: A Preliminary Study.Neuropsychopharmacology reports · 2025Article
- A Comprehensive Review of Current and Emerging Treatments for Narcolepsy Type 1.Journal of clinical medicine · 2025Review
- Narcolepsy and rapid eye movement sleep.Journal of sleep research · 2025Review
- Orexin Neurons to Sublaterodorsal Tegmental Nucleus Pathway Prevents Sleep Onset REM Sleep-Like Behavior by Relieving the REM Sleep Pressure.Research (Washington, D.C.) · 2024Article
- Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis.Journal of pharmaceutical analysis · 2023Article
- Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice.Journal of sleep research · 2023Article
- Recent advances in neuropeptide-related omics and gene editing: Spotlight on NPY and somatostatin and their roles in growth and food intake of fish.Frontiers in endocrinology · 2022Review
- A Century Searching for the Neurons Necessary for Wakefulness.Frontiers in neuroscience · 2022Review
- MicroRNA-139-5p Promotes Functional Recovery and Reduces Pain Hypersensitivity in Mice with Spinal Cord Injury by Targeting Mammalian Sterile 20-like Kinase 1.Neurochemical research · 2021Article
- Hypocretin/Orexin Receptor Pharmacology and Sleep Phases.Frontiers of neurology and neuroscience · 2021Review
- Hypocretin (Orexin) Replacement Therapies.Medicine in drug discovery · 2020Article
- Role of spontaneous and sensory orexin network dynamics in rapid locomotion initiation.Progress in neurobiology · 2020Article
- Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment.Nature reviews. Neurology · 2019Review
- Recent advances in treatment for narcolepsy.Therapeutic advances in neurological disorders · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Narcolepsy-cataplexy is a chronic neurological disorder caused by loss of orexin (hypocretin)-producing neurons, associated with excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucinations, and fragmentation of nighttime sleep. Currently, human narcolepsy is treated by providing symptomatic therapies, which can be associated with an array of side effects. Although peripherally administered orexin does not efficiently penetrate the blood-brain barrier, centrally delivered orexin can effectively alleviate narcoleptic symptoms in animal models. Chronic intrathecal drug infusion through an implantable pump is a clinically available strategy to treat a number of neurological diseases. Here we demonstrate that the narcoleptic symptoms of orexin knockout mice can be reversed by lumbar-level intrathecal orexin delivery. Orexin was delivered via a chronically implanted intrathecal catheter at the upper lumbar level. The computed tomographic scan confirmed that intrathecally administered contrast agent rapidly moved from the spinal cord to the brain. Intrathecally delivered orexin was detected in the brain by radioimmunoassay at levels comparable to endogenous orexin levels. Cataplexy and sleep-onset REM sleep were significantly decreased in orexin knockout mice during and long after slow infusion of orexin (1 nmol/1 µL/h). Sleep/wake states remained unchanged both quantitatively as well as qualitatively. Intrathecal orexin failed to induce any changes in double orexin receptor-1 and -2 knockout mice. This study supports the concept of intrathecal orexin delivery as a potential therapy for narcolepsy-cataplexy to improve the well-being of patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.