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MeSH: narkolepsie-chemicky indukované

7 záznamů v Medvik Filtry

Článek

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy

Ollila, Hanna M
Autor Ollila, Hanna M Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
Sharon, Eilon
Autor Sharon, Eilon ORCID Department of Genetics, Stanford University, Stanford, CA, 94305, USA Department of Biology, Stanford University, Stanford, CA, 94305, USA
Lin, Ling
Autor Lin, Ling Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA
Sinnott-Armstrong, Nasa
Autor Sinnott-Armstrong, Nasa ORCID Department of Genetics, Stanford University, Stanford, CA, 94305, USA Department of Biology, Stanford University, Stanford, CA, 94305, USA
Ambati, Aditya
Autor Ambati, Aditya ORCID Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA
Yogeshwar, Selina M
Autor Yogeshwar, Selina M Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA Department of Neurology, Charité-Universitätsmedizin, 10117, Berlin, Germany Charité-Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, 10117, Berlin, Germany
Hillary, Ryan P
Autor Hillary, Ryan P Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA
Jolanki, Otto
Autor Jolanki, Otto ORCID Department of Genetics, Stanford University, Stanford, CA, 94305, USA
Faraco, Juliette
Autor Faraco, Juliette Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA
Einen, Mali
Autor Einen, Mali Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA

Nature communications. 2023 ; 14 (1) : 2709. [pub] 20230515

Nat Commun
ISSN 2041-1723
Medvik
Zdroj

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

MeSH
autoimunita genetika MeSH
autoimunitní nemoci * epidemiologie genetika MeSH
chřipka lidská * epidemiologie genetika MeSH
lidé MeSH
narkolepsie * chemicky indukované genetika MeSH
vakcíny proti chřipce * škodlivé účinky MeSH
virus chřipky A, podtyp H1N1 * genetika MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Extramural MeSH

Článek

Changes in Cataplexy Frequency in a Clinical Trial of Lower-Sodium Oxybate with Taper and Discontinuation of Other Anticataplectic Medications

CNS drugs. 2022 ; 36 (6) : 633-647. [pub] 20220530

CNS Drugs
ISSN 1179-1934
Medvik
Zdroj

BACKGROUND: Lower-sodium oxybate (LXB) is an oxybate medication with the same active moiety as sodium oxybate (SXB) and a unique composition of cations, resulting in 92% less sodium. LXB was shown to improve cataplexy and excessive daytime sleepiness in people with narcolepsy in a placebo-controlled, double-blind, randomized withdrawal study (NCT03030599). Additional analyses of data from this study were conducted to explore the effects of LXB on cataplexy, including the clinical course and feasibility of transition from other anticataplectics to LXB monotherapy. OBJECTIVE: The aim of these analyses was to evaluate cataplexy frequency during initiation/optimization of LXB and taper/discontinuation of prior antidepressant/anticataplectic medications. METHODS: Eligible participants (adults aged 18-70 years with narcolepsy with cataplexy) entered the study taking SXB only (group A), SXB + other anticataplectics (group B), or anticataplectic medication other than SXB (group C), or were cataplexy-treatment naive (group D). LXB was initiated/optimized during a 12-week, open-label, optimized treatment and titration period (OLOTTP). Other anticataplectics were tapered/discontinued during weeks 3-10 of OLOTTP. A 2-week stable-dose period (SDP; during which participants took a stable dose of open-label LXB) and 2-week double-blind randomized withdrawal period (during which participants were randomized to continue LXB treatment or switch to placebo) followed OLOTTP. Treatment-emergent adverse events (TEAEs) were recorded throughout the duration of the study. RESULTS: At the beginning of OLOTTP, median weekly cataplexy attacks were lower in participants taking SXB at study entry (SXB only [2.00]; SXB + other anticataplectics [0.58]) versus participants who were taking other anticataplectics (3.50) or were anticataplectic naive (5.83). Median weekly cataplexy attacks decreased during weeks 1-2 of OLOTTP in all groups. Increased cataplexy frequency was observed in participants tapering/discontinuing other anticataplectics during weeks 3-10 and was more prominent in participants taking other anticataplectics alone compared with those taking SXB plus other anticataplectics. Cataplexy frequency decreased throughout initiation/optimization in anticataplectic-naive participants. Median number of cataplexy-free days/week at the end of SDP (study week 14) was similar in all groups (6.0, 6.1, 6.0, and 6.2 in groups A, B, C, and D, respectively). During OLOTTP and SDP, TEAEs of worsening cataplexy were reported in 0%, 47.8%, 16.7%, and 2.2% of participants in groups A, B, C, and D, respectively; most TEAEs of worsening cataplexy were reported during tapering/discontinuation of other anticataplectics. CONCLUSIONS: LXB monotherapy was effective in reducing cataplexy and increasing cataplexy-free days. These results illustrate the feasibility of switching from SXB to LXB while tapering/discontinuing other anticataplectics. TRIAL REGISTRATION: A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy; https://clinicaltrials.gov/ct2/show/NCT03030599 ; clinicaltrials.gov identifier: NCT03030599.

MeSH
dospělí MeSH
dvojitá slepá metoda MeSH
kataplexie * farmakoterapie MeSH
lidé MeSH
narkolepsie * chemicky indukované farmakoterapie MeSH
oxybát sodný * škodlivé účinky MeSH
poruchy nadměrné spavosti * farmakoterapie MeSH
Check Tag
dospělí MeSH
lidé MeSH
Publikační typ
časopisecké články MeSH
randomizované kontrolované studie MeSH

Článek

Narkolepsii spustily protilátky proti virovému proteinu

Petr, Jaroslav, 1958-
Autor Autorita ORCID

Medical tribune. 2015 ; 11 (21) : D5.

Med. Trib. (Praha)
ISSN 1214-8911
Medvik
Zdroj

Článek

Antidepressants substantially affect basic REM sleep characteristics in narcolepsy-cataplexy patients

Neuro-endocrinology letters. 2015 ; 36 (5) : 430-433.

Neuro-endocrinol. lett.
ISSN 0172-780X
Medvik
Zdroj

OBJECTIVES: Antidepressants substantially affect REM sleep characteristics and trigger manifestations of REM sleep behavior disorder (RBD) in the general, non-narcoleptic, population. Antidepressants are also frequently administrated in an attempt to suppress cataplexy. We investigated the role of antidepressants in the development of RBD in narcolepsy with cataplexy (NC) patients. PATIENTS/METHODS: Seventy-five patients diagnosed with NC were assessed by a structured interview (focused on RBD manifestations and the use of antidepressants) and night video-polysomnography followed by the multiple sleep latency test. RESULTS: Of all 75 NC patients (36 male, 39 female; mean age 46.1±18.5 years), 34 cases had a history of antidepressant use (45.3%; 18 male, 16 female). In this antidepressant-positive group, 13 patients suffered from RBD (38.2%). Among antidepressant-naïve patients, only 5 subjects (12.2%) were diagnosed with RBD. Polysomnographic data showed significantly increased REM latency (p<0.01) and reduced percentage of REM sleep (p<0.01) in the antidepressant-positive group, as well as more periodic limb movements during sleep (p=0.01). CONCLUSIONS: NC patients with a history of antidepressant use showed a three-fold higher occurrence of RBD in comparison to antidepressant-naïve patients.