Gene Expression Signatures to Predict Treatment Response in Systemic Sclerosis

预测系统性硬化症治疗反应的基因表达特征

• 批准号: 8834415
• 负责人: MICHAEL W FANGER
• 金额: $ 63.91万
• 依托单位: CELDARA MEDICAL, LLC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-06 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8834415
• 关键词: Adverse effects; Algorithms; Archives; Autoantibodies; Autoimmune Diseases; Biochemical Pathway; Bioinformatics; Biological Markers; Biopsy; Blood Vessels; Cellcept; Classification; Clinical; Clinical Course of Disease; Clinical Trials; DNA Microarray Chip; Development; Diagnosis; Diagnostic; Disease; Enrollment; Etiology; Exposure to; Fibrosis; Freezing; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genes; Gleevec; Goals; Gold; Health; Heart; Hereditary Disease; Heterogeneity; Imatinib mesylate; Immunosuppressive Agents; Individual; Inflammatory; Laboratories; Lung; Maps; Measures; Molecular; Molecular Profiling; Nature; Observational Study; Organ; Outcome; Outcome Measure; Paraffin Embedding; Pathogenesis; Pathway interactions; Patient Selection; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physicians; Pilot Projects; Publishing; Relative (related person); Research Design; Risk; Sampling; Scleroderma; Services; Signal Pathway; Skin; Systemic Scleroderma; Testing; Translating; Tyrosine Kinase Inhibitor; Validation; Work; base; clinical phenotype; cohort; cost; design; drug development; effective therapy; effectiveness trial; efficacy trial; improved; insight; lymphocyte proliferation; malignant breast neoplasm; mycophenolate mofetil; nano-string; novel; novel diagnostics; open label; patient population; prospective; research clinical testing; response; risk benefit ratio; standard of care; technology development; tool; treatment planning; treatment response

DESCRIPTION (provided by applicant): Today, systemic sclerosis (SSc) clinical trials generally include all subsets; some may benefit, others do not, confounding measures of efficacy. Because each expression subset has a different underlying deregulated molecular pathway, no single drug is expected to benefit all patients i.e. rational patient selection is required to facilitate drug development. Further, a quantitative measure of clinical outcome and endpoints will enable a scientific measure of trial effectiveness and avoid the difficulties associated with the cyclic nature of SSc. For example, response to imatinib mesylate (Gleevec(R)), a tyrosine kinase inhibitor and to mycophenolate mofetil (Cellcept), an attenuator of lymphocyte proliferation, can be quantitatively measured by gene expression. Finally, insights into the molecular pathways defining each subtype will enable us to identify and potentially design new drugs. Beyond drug development, subtyping will help individual patients and their doctors by allowing an individualized treatment plan informed by each patient's subtype. Together, these benefits are both exciting and compelling, and are fundamentally changing what it means to be diagnosed with SSc. This work will provide insights into the pathogenesis of the disease that may influence the development of new treatments by other groups or pharmaceutical companies. The immediate result of this study is the validation and prospective clinical testing of gene expression biomarkers on a new platform for predicting treatment response in SSc. Development of this technology into a clinical diagnostic tool and service will significantly improve the management and ultimately the health of patients with SSc.

描述（由申请人提供）：今天，系统性硬化症（SSc）临床试验通常包括所有子集;一些可能受益，另一些则没有，混淆疗效指标。由于每个表达亚群具有不同的潜在失调分子途径，因此预计没有单一药物可使所有患者受益，即需要合理的患者选择以促进药物开发。此外，临床结局和终点的定量测量将使试验有效性的科学测量成为可能，并避免与SSc的周期性相关的困难。例如，对甲磺酸伊马替尼（Gleevec（R））（一种酪氨酸激酶抑制剂）和对吗替麦考酚酯（Cellcept）（一种淋巴细胞增殖的衰减剂）的应答可以通过基因表达来定量测量。最后，深入了解定义每个亚型的分子途径将使我们能够识别和潜在地设计新药。除了药物开发之外，亚型将通过允许根据每个患者的亚型制定个性化治疗计划来帮助个体患者及其医生。总之，这些好处既令人兴奋又令人信服，并从根本上改变了被诊断患有SSc的意义。这项工作将提供深入了解疾病的发病机制，可能会影响其他团体或制药公司开发新的治疗方法。这项研究的直接结果是在一个新的平台上对基因表达生物标志物进行验证和前瞻性临床测试，以预测SSc的治疗反应。将这项技术发展为临床诊断工具和服务将显着改善SSc患者的管理并最终改善其健康。