Abstract
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, we performed a clinical trial administering l-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). l-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. l-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo. This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients.Trial RegistrationUniversity hospital Medical Information Network (UMIN) UMIN000003760
Highlights
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities
A total of 30 narcolepsy patients were enrolled in this study between May, 2010 and July, 2010
There were no significant improvements in Japanese version of the Epworth Sleepiness Scale (JESS) and SF-36 subscale scores between L-carnitine and placebo periods
Summary
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy (sudden loss of muscle tone in response to strong emotions), and rapid eye movement (REM) sleep abnormalities. Following studies in dogs [8] and mice [9], a 95% loss of orexin (hypocretin)-producing cells in postmortem hypothalami from narcolepsy patients was reported [10,11]. Results from a genome-wide association study (GWAS) have revealed significant associations between narcolepsy and single nucleotide polymorphisms (SNP) located in the T-cell receptor a-locus and P2RY11 [14,15]. We conducted a GWAS and identified a novel narcolepsy-related SNP (rs5770917), located adjacent to the gene encoding carnitine palmitoyltransferase 1B (CPT1B) [16]. The mRNA expression levels of CPT1B were associated with this SNP and the expression levels were decreased according to the number of risk alleles (C) [16,17]
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