Anti-Norepinephrine Transporter monoclonal antibody, clone OFU-06

The objective of the Genome-based Therapeutic Drugs for Depression study is to investigate the function of variations in genes encoding key proteins in serotonin, norepinephrine, neurotrophic and glucocorticoid signaling in determining the response to serotonin-reuptake-inhibiting and norepinephrine-reuptake-inhibiting antidepressants. A total of 116 single nucleotide polymorphisms in 10 candidate genes were genotyped in 760 adult patients with moderate-to-severe depression, treated with escitalopram (a serotonin reuptake inhibitor) or nortriptyline (a norepinephrine reuptake inhibitor) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models. Several variants in a serotonin receptor gene (HTR2A) predicted response to escitalopram with one marker (rs9316233) explaining 1.1% of variance (P = 0.0016). Variants in the norepinephrine transporter gene (SLC6A2) predicted response to nortriptyline, and variants in the glucocorticoid receptor gene (NR3C1) predicted response to both antidepressants. Two HTR2A markers remained significant after hypothesis-wide correction for multiple testing. A false discovery rate of 0.106 for the three strongest associations indicated that the multiple findings are unlikely to be false positives. The pattern of associations indicated a degree of specificity with variants in genes encoding proteins in serotonin signaling influencing response to the serotonin-reuptake-inhibiting escitalopram, genes encoding proteins in norepinephrine signaling influencing response to the norepinephrine-reuptake-inhibiting nortriptyline and a common pathway gene influencing response to both antidepressants. The single marker associations explained only a small proportion of variance in response to antidepressants, indicating a need for a multivariate approach to prediction. The Pharmacogenomics Journal (2009) 9, 225-233; doi: 10.1038/tpj.2009.12; published online 14 April 2009

Context. Fatigue is a common problem in oncology patients. Less is known about decrements in energy levels and the mechanisms that underlie both fatigue and energy. Objectives. In patients with breast cancer, variations in neurotransmitter genes between lower and higher fatigue latent classes and between the higher and lower energy latent classes were evaluated. Methods. Patients completed assessments before and monthly for six months after surgery. Growth mixture modeling was used to identify distinct latent classes for fatigue severity and energy levels. Thirty candidate genes involved in various aspects of neurotransmission were evaluated. Results. Eleven single-nucleotide polymorphisms or haplotypes (i. e., ADRB2 rs1042718, BDNF rs6265, COMT rs9332377, CYP3A4 rs4646437, GALR1 rs949060, GCH1 rs3783642, NOS1 rs9658498, NOS1 rs2293052, NPY1R Haplotype A04, SLC6A2 rs17841327, and 5HTTLPR + rs25531 in SLC6A4) were associated with latent class membership for fatigue. Seven singlenucleotide polymorphisms or haplotypes (i. e., NOS1 rs471871, SLC6A1 rs2675163, SLC6A1 Haplotype D01, SLC6A2 rs36027, SLC6A3 rs37022, SLC6A4 rs2020942, and TAC1 rs2072100) were associated with latent class membership for energy. Three of 13 genes (i. e., NOS1, SLC6A2, and SLC6A4) were associated with latent class membership for both fatigue and energy. Conclusions. Molecular findings support the hypothesis that fatigue and energy are distinct, yet related symptoms. Results suggest that a large number of neurotransmitters play a role in the development and maintenance of fatigue and energy levels in breast cancer patients. (C) 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.