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Blood transcriptomic biomarkers of Alzheimer's disease patients treated with EHT 0202.
J Alzheimers Dis ; 34(2): 469-83, 2013.
Article em En | MEDLINE | ID: mdl-23234880
ABSTRACT
Monitoring the genomic expression of patients in clinical trials for Alzheimer's disease (AD) can assist trial design and treatment response analysis. Here, we report on the identification in AD patients of blood-based transcriptomic signatures associated with treatment response of EHT 0202, a new compound with potential disease-modifying and symptomatic properties, in a 3-month, placebo-controlled, Phase IIA study aimed at determining the clinical safety, tolerability, and exploratory efficacy of EHT 0202 (40 and 80 mg bid) as adjunctive therapy to one cholinesterase inhibitor in mild to moderate AD patients. Genome-wide transcriptomic profiling was performed on blood samples taken prior to treatment and at study completion in a subpopulation of 60 AD patients selected as either the 10 worst disease decliners or the 10 best improvers of each treatment group, using ADAS-Cog scores as measure of disease severity. In the patients responding to EHT 0202, a pre-treatment (baseline) transcriptomic signature showed activation of pathways related to AD, CNS disorders, diabetes, inflammation, and autoimmunity, while a post-treatment signature indicated reduced activation of these pathways with induced metabolic and transcription stimulation. This pilot study demonstrates the utility of blood transcriptomic signatures used as biomarkers for predicting patient response or monitoring efficacy, for an administered therapeutic drug in a complex disease such as AD. For EHT 0202 or other AD drugs, such biomarkers may help to improve strategies to better identify appropriate patient populations for treatment, understand the drug mechanism of efficacy, and/or clarify the inherent subjectivity in most clinical endpoints used in this disease.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Inibidores da Colinesterase / Doença de Alzheimer / Transcriptoma Tipo de estudo: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Inibidores da Colinesterase / Doença de Alzheimer / Transcriptoma Tipo de estudo: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: França