New applications of disease genetics and pharmacogenetics to drug development

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• 作者：Allen D Roses¹ ; ² ; ^{roses@zinfandelpharma.com" class="auth_mail} ; ^{allen.roses@duke.edu" class="auth_mail} ; Ann M Saunders² ; Michael W Lutz² ; Nanyin Zhang³ ; Ahmad R Hariri² ; Karen E Asin⁴ ; Donna G Crenshaw¹ ; Kumar Budur⁴ ; Daniel K Burns¹ ; Stephen K Brannan⁴
• 刊名：Current Opinion in Pharmacology
• 出版年：February, 2014
• 年：2014
• 卷：14
• 期：Complete
• 页码：81-89
• 全文大小：1323 K

文摘

TOMMORROW is a Phase III delay of onset clinical trial to determine whether low doses of pioglitazone, a molecule that induces mitochondrial doubling, delays the onset of MCI-AD in normal subjects treated with low dose compared to placebo. BOLD imaging studies in rodents and man were used to find the dose that increases oxygen consumption at central regions of the brain in higher proportion than activation of large corticol regions. The trial is made practical by the use of a pharmacogenetic algorithm based on TOMM40 and APOE genotypes and age to identify normal subjects at high risk of MCI-AD between the ages of 65-83 years within a five year follow-up period.