Genetic Screen for Antipsychotic Drug Response

描述（由申请人提供）：精神分裂症是最严重的精神障碍，折磨着1%的人口，给患者及其家属造成痛苦，并最大限度地消耗了医疗资源。加布里埃尔制药的使命是通过基因、药理学和其他技术改善精神疾病患者的治疗和保健。该基金的主要目标是建立抗精神病药物反应的遗传筛选和精神分裂症预后的遗传预测因子，从而实现个性化的治疗方法和资源分配。本提案描述了i期引入的交互式临床信息和DNA数据库（CI-DNA）的基本原理、设计和科学发展。CI-DNA数据库将扩展到包括两个用于药物遗传学分析的药理学数据库组件和一个用于遗传预测分析的精神分裂症临床结果数据库。第一阶段成功地开发了氯氮平药物遗传学数据库的临床部分。作为I期可行性研究的一部分，Gabriel Pharma首次建立了氯氮平阴性症状反应的遗传预测因子。在第二阶段，扩展数据库中的受试者将对10个功能性候选基因变体进行基因分型。选择这些基因是因为它们与中枢神经系统（CNS）、精神分裂症和抗精神病药物机制的关系。此外，将在数据库中检查最近发现的三个精神分裂症易感基因。完全开发的专有CI-DNA数据库系统是一项独特的创新，通过内部和合作的科学努力，可以建立抗精神病药物反应和精神分裂症结果的遗传筛选。这项工作有可能影响精神分裂症患者个体以及相关卫生保健服务的更广泛需求。

DESCRIPTION (provided by applicant): Schizophrenia, the most serious of the mental disorders, afflicts 1% of the population, causing suffering to patients and their families and stretching health care resources to a maximum. It is the mission of Gabriel Pharma to improve the treatment and health care for patients with mental illnesses through genetic, pharmacological and other technologies. A primary goal of this grant is to establish a genetic screen for antipsychotic drug response and genetic predictors of outcome of schizophrenia, enabling an individualized approach to treatment and resource allocation. This proposal describes the rationale, design and scientific development of the Interactive Clinical Information and DNA database (CI-DNA) introduced in Phase I. The CI-Database will be expanded to include two pharmacological database components designed for pharmacogenetics analysis and a first-of-its-kind clinical outcome database for schizophrenia designed for genetic predictor analysis. Phase I successfully developed the clinical portion of a database for the pharmacogenetics of clozapine. As part of the Phase I feasibility study Gabriel Pharma established, for the first time, genetic predictors of negative symptom response to clozapine. In Phase II, subjects in the expanded database will be genotyped for a panel of ten functional candidate gene variants. These genes are chosen for their relationship to the central nervous system (CNS), schizophrenia and antipsychotic drug mechanisms. In addition, three recently discovered schizophrenia susceptibility genes will be examined in the database. The fully developed proprietary CI-DNA database system is a unique innovation enabling the establishment of genetic screens for antipsychotic drug response and schizophrenia outcome through internal and collaborative scientific efforts. This work has the potential of impacting the individual patient with schizophrenia as well as broader needs in related health care delivery.