Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1

Dauvilliers, Yves; Mignot, Emmanuel; Rio-Villegas, Rafael del; Du, Yeting; Hanson, Elizabeth; Inoue, Yuichi; Kadali, Harisha; Koundourakis, Elena; Meyer, Seetha; Rogers, Raquel; Scammell, Thomas E.; Sheikh, Sarah; Swick, Todd J.; Szakács, Zsolt; Rosenstiel, Philipp von; Wu, Jingtao; Zeitz, H; Murthy, Naga Venkatesha; Plazzi, Giuseppe; Hehn, Christian von

doi:10.1056/nejmoa2301940

Cited by 31 publications

(7 citation statements)

References 28 publications

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“…Recent work demonstrates the benefit of this new class of medications in controlled studies, mainly in patients with narcolepsy type I but with liver toxicity. 54 62 …”

Section: Treatmentmentioning

confidence: 99%

“… 11 New medications such as orexin agonists are promising to improve the quality of life of these patients. 62 …”

Section: Treatmentmentioning

confidence: 99%

“…Recent work demonstrates the benefit of this new class of medications in controlled studies, mainly in patients with narcolepsy type I but with liver toxicity. 54,62 Cataplexy can be treated with tricyclic and other classes of antidepressants such as citalopram, fluoxetine, and venlafaxine. The drug that has also been successfully used to control cataplexy is sodium oxybate or hydroxybutyric acid, which is not available in Brazil.…”

Section: Treatmentmentioning

confidence: 99%

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Narcolepsy: an interface among neurology, immunology, sleep, and genetics

Coelho

2024

Arq Neuropsiquiatr

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Narcolepsy is a primary disorder of the central nervous system resulting from genetic, environmental, and immunological interactions defined as excessive daytime sleepiness plus cataplexy, hallucinations, sleep paralysis, and sleep fragmentation. The pathophysiology is not entirely known, but the interaction among genetic predisposition, environmental exposition, and immune component with consequent hypocretin-1 deficiency is the model to explain narcolepsy type I. The mechanism of narcolepsy type II is less understood. There is a delay of over ten years for the diagnosis of narcolepsy around the world. Patients with narcolepsy have many comorbidities with a negative impact on quality of life. The treatment of narcolepsy must contain an educational approach for the family, coworkers, and patients. Scheduled naps and sleep hygiene are essential to minimize the dose of medications. Much progress has been seen in the pharmacological treatment of narcolepsy with new stimulants, different presentations of oxybate, and recent studies with orexin agonists. Narcolepsy is a rare disease that needs to be more understood and highlighted to avoid delayed diagnosis and severe disabilities in patients.

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“…Recent work demonstrates the benefit of this new class of medications in controlled studies, mainly in patients with narcolepsy type I but with liver toxicity. 54 62 …”

Section: Treatmentmentioning

confidence: 99%

“… 11 New medications such as orexin agonists are promising to improve the quality of life of these patients. 62 …”

Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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Narcolepsy: an interface among neurology, immunology, sleep, and genetics

Coelho

2024

Arq Neuropsiquiatr

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“…Future directions: Selective orexin receptor agonists are a promising new class of drugs. Recent pilot trials on orexin receptor agonists (TAK-994, TAK-861) indicated a significant improvement in EDS and cataplexy [62]. Other histaminergic drugs and drugs also acting on the orexin system (i.e., mazindol) are under development [63].…”

Section: Central Disorders Of Hypersomnolence (Cdh)mentioning

confidence: 99%

Pharmacological Treatments of Sleep–Wake Disorders: Update 2023

Kallweit,

Kallweit

2023

CTN

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Biological, environmental, behavioral, and social factors can influence sleep and lead to sleep disorders or diseases. Sleep disorders are common, numerous, and heterogeneous in terms of their etiology, pathogenesis, and symptomatology. The management of sleep–wake circadian disorders (SWCDs) includes education on sleep hygiene, behavioral strategies, psychotherapy (cognitive behavioral therapy (CBT), particularly), instrument-based treatments (i.e., positive airway pressure therapy, hypoglossal nerve stimulation), and pharmacotherapy. Depending on the disease, therapy varies and is executed sequentially or can be a combination of several forms of therapy. Drugs used for SWCDs include traditional sleep- or wake-promoting agents and chronotherapeutic agents. Recently, novel medications, which more precisely act on specific neurochemical systems (i.e., the orexin system) important for sleep and waking, are also increasingly being used. In this review, the pharmacotherapy of common sleep disorders (insomnia, sleep-related breathing disorder, central disorders of hypersomnolence, circadian rhythm sleep–wake disorders, parasomnias, and sleep-related movement disorders) embedded in the overall therapeutic concept of each disorder is presented. There is also an outlook on possible future pharmacotherapies.

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“…NT1 is attributed to a marked and selective loss of orexin-producing neurons in the lateral hypothalamus [3,4]. Diagnosis typically occurs several years after the onset of clinical symptoms and relies on an invasive procedure measuring the orexin level in the cerebral spinal fluid (CSF) [5][6][7]. Although assessing the sleep cycle can aid in diagnosing NT1, it may sometimes be confounded with other sleep disorders.…”

Section: Introductionmentioning

confidence: 99%

Absence of specific autoantibodies in patients with narcolepsy type 1 as indicated by an unbiased random peptide-displayed phage screening

Tran,

Nguyen,

Dauvilliers

et al. 2024

PLoS ONE

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Narcolepsy type 1 (NT1) is an enigmatic sleep disorder characterized by the selective loss of neurons producing orexin (also named hypocretin) in the lateral hypothalamus. Although NT1 is believed to be an autoimmune disease, the orexinergic neuron-specific antigens targeted by the pathogenic immune response remain elusive. In this study, we evaluated the differential binding capacity of various peptides to serum immunoglobin G from patients with NT1 and other hypersomnolence complaints (OHCs). These peptides were selected using an unbiased phage display technology or based on their significant presence in the serum of NT1 patients as identified from previous studies. Although the subtractive biopanning strategy successfully enriched phage clones with high reactivity against NT1 serum IgG, the 101 randomly selected individual phage clones could not differentiate the sera from NT1 and OHC. Compared to the OHC control group, serum from several NT1 patients exhibited increased reactivity to the 12-mer peptides derived from TRBV7, BCL-6, NRXN1, RXRG, HCRT, and RTN4 proteins, although not statistically significant. Collectively, employing both unbiased and targeted methodologies, we were unable to detect the presence of specific autoantibodies in our NT1 patient cohort. This further supports the hypothesis that the autoimmune response in NT1 patients likely stems primarily from T cell-mediated immunity rather than humoral immunity.

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Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1

Cited by 31 publications

References 28 publications

Narcolepsy: an interface among neurology, immunology, sleep, and genetics

Narcolepsy: an interface among neurology, immunology, sleep, and genetics

Pharmacological Treatments of Sleep–Wake Disorders: Update 2023

Absence of specific autoantibodies in patients with narcolepsy type 1 as indicated by an unbiased random peptide-displayed phage screening

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