Pharmacogenetics and treatment response in narcolepsy type 1: Relevance of the polymorphisms of the drug transporter gene abcb1

Monica Moresco, Laura Natalia Riccardi, Fabio Pizza, Corrado Zenesini, Leonardo Caporali, Giuseppe Plazzi, Susi Pelotti

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Narcolepsy type 1 (NT1) is a chronic hypersomnia clinically characterized by daytime sleepiness and cataplexy. Narcolepsy type 1 treatments target individual symptoms: wake-promoting agents (eg, modafinil) are effective for sleepiness, antidepressants (eg, venlafaxine) on cataplexy, whereas sodium oxybate on both. Narcolepsy type 1 patients variably respond to modafinil and venlafaxine independently of individual clinical features. Given the potential influence of drug transmembrane transport (glycoprotein-P) on drug response, we explored the relation between genetic polymorphisms in the ABCB1 gene and clinical response to modafinil/venlafaxine in NT1. Methods: Individual drug response and genotypes were assessed in 107 NT1 patients (males/females, 64/43; mean age, 38 ± 21 years) treated with modafinil and/or venlafaxine at stable doses for at least 3 months. Minisequencingwas performed to detect single-nucleotide polymorphisms in ABCB1. Patients with different responses to treatment were contrasted by Fisher exact test and multivariate analysis. Results: The ABCB1 diplotype was significantly associated with clinical response to modafinil, with the CGC-TTT (1236/2677/3435) being more frequent in the modafinil responder versus nonresponder group (P = 0.013). Conversely, no significant associations with clinical response to venlafaxine were found. Conclusions: The ABCB1 variants modulate therapeutic response to modafinil and may partly explain pharmacoresistance in NT1 patients.

Original languageEnglish
Pages (from-to)18-23
Number of pages6
JournalClinical Neuropharmacology
Volume39
Issue number1
DOIs
Publication statusPublished - 2016

Keywords

  • ABCB1 polymorphisms
  • Drug efficacy
  • Modafinil
  • Narcolepsy type 1
  • Pharmacogenetics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Clinical Neurology

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