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Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia

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 rs73304...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810388/
https://www.ncbi.nlm.nih.gov/pubmed/26861400
http://dx.doi.org/10.3390/jpm6010009
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author 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
author_facet 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
author_sort Nisenbaum, Laura K.
collection PubMed
description 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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spelling pubmed-48103882016-04-04 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 J Pers Med Article 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. MDPI 2016-02-05 /pmc/articles/PMC4810388/ /pubmed/26861400 http://dx.doi.org/10.3390/jpm6010009 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia
title Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia
title_full Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia
title_fullStr Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia
title_full_unstemmed Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia
title_short Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia
title_sort serotonin 2a receptor snp rs7330461 association with treatment response to pomaglumetad methionil in patients with schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810388/
https://www.ncbi.nlm.nih.gov/pubmed/26861400
http://dx.doi.org/10.3390/jpm6010009
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