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Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia.
Nisenbaum, Laura K; Downing, AnnCatherine M; Zhao, Fangyi; Millen, Brian A; Munsie, Leanne; Kinon, Bruce J; Adams, David H; Gomez, Juan Carlos; Penny, Michelle Ann.
Afiliação
  • Nisenbaum LK; Eli Lilly and Company, Indianapolis, IN 46285, USA. .nisenbaum@lilly.com.
  • Downing AM; Eli Lilly and Company, Indianapolis, IN 46285, USA. downing_anncatherine_m@lilly.com.
  • Zhao F; Eli Lilly and Company, Indianapolis, IN 46285, USA. zhao_fangyi@lilly.com.
  • Millen BA; Eli Lilly and Company, Indianapolis, IN 46285, USA. millen_brian_a@lilly.com.
  • Munsie L; Eli Lilly and Company, Indianapolis, IN 46285, USA. munsie_leanne_m@lilly.com.
  • Kinon BJ; Lundbeck LLC, Four Parkway North, Deerfield, IL 60015, USA. BKIN@lundbeck.com.
  • Adams DH; Eli Lilly and Company, Indianapolis, IN 46285, USA. adams_david_henry@lilly.com.
  • Gomez JC; Eli Lilly and Company, Indianapolis, IN 46285, USA. gomez_juan-carlos@lilly.com.
  • Penny MA; Computational Biology and Genomics, Biogen, 225 Binney Street, Cambridge, MA 02142, USA. michelle.penny@biogen.com.
J Pers Med ; 6(1)2016 Feb 05.
Article em En | MEDLINE | ID: mdl-26861400
ABSTRACT
This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A receptor gene compared to A/A homozygous patients. The effect of the rs7330461 genotype on the response to pomaglumetad methionil treatment was assessed in three additional clinical trials and in an integrated analysis. Overall, this study includes data from 1115 Caucasian patients for whom genotyping information for rs7330461 was available, consisting of 513 A/A homozygous, 466 A/T heterozygous and 136 T/T homozygous patients. Caucasian T/T homozygous patients showed significantly (p ≤ 0.05) greater improvement in Positive and Negative Syndrome Scale (PANSS) total scores during treatment with pomaglumetad methionil 40 mg twice daily compared to A/A homozygous patients. Additionally, T/T homozygous patients receiving pomaglumetad methionil had significantly (p ≤ 0.05) greater improvements in PANSS total scores compared to placebo and similar improvements as T/T homozygous patients receiving standard-of-care (SOC) treatment. The findings reported here in conjunction with prior reports show that in Caucasian patients with schizophrenia, the T/T genotype at rs7330461 is consistently associated with an increased treatment response to pomaglumetad methionil compared to the A/A genotype.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Risk_factors_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Risk_factors_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article