Using a novel model of antidepressant efficacy to discover new compounds and personalized treatments.

世界卫生组织估计，到2020年，严重抑郁障碍(MDD)将成为 世界范围内最常见的残疾原因。尽管大约六分之一的美国人会患上MDD 在他们的一生中，许多MDD患者在初级保健环境中没有得到诊断，20%的患者 误诊为MDD。鉴于MDD涉及巨大的医疗、经济和社会成本， 非常需要一种简单、客观的生物标记物试验来帮助临床医生准确识别MDD。 目前还没有一种测试可以准确诊断MDD并将其与其他精神疾病区分开来。 此外，抗抑郁治疗的临床反应需要长达两个月的时间。有巨大的需求 一种可以在治疗开始后几天内预测反应的测试。中国的潜在市场 一项准确的MDD诊断测试每年估计要花费50-80亿美元。医疗服务的付款人将覆盖 这种诊断测试的成本，因为准确地识别和治疗MDD将降低高 向未经治疗的抑郁症患者提供医疗服务所产生的医疗成本以及改善 糖尿病或心脏病等合并疾病患者的预后。 MDD诊断测试的另一个市场是制药公司。这些公司拥有 一致退出了情绪障碍的发现努力，部分原因是许多 临床试验。这些失败的部分原因是招收了不适当的患者。客观的测试 千年发展目标办公室可以通过对招募对象的适当性提供确定性来解决这一关切。 Pax神经科学诊断生物标记物GαS隔离试验表明 与非抑郁症患者相比，患者在脂筏中捕获GαS的比例明显更高 控制并能够准确地识别患有MDD的患者。Pax使用的原则与 GSA制定了C6胶质瘤(G、α、S、绿色荧光蛋白)FRAP检测方法，可以可靠地预测抗抑郁药的疗效。 拟议的研究将把化验结果转换为高含量筛选(HCS)格式，从而实现高含量筛选 寻找针对MDD的新型小分子的运动。此外，我们还将开发一个二级屏幕，使用 神经干细胞，来自L S和S S的已知反应的受试者 抗抑郁药(SSRI)，以确认筛查的疗效。此辅助屏幕可以修改为 评估MDD患者的治疗效果。这是一个令人兴奋的提议，它提供了一种基础技术 既可以找到新药，也可以开发个性化的抑郁症治疗方法。

The World Health Organization estimates that by 2020, major depressive disorder (MDD) will be the most common cause of disability, worldwide. Although approximately 1 in 6 Americans will suffer from MDD during their lifetime, many patients with MDD go undiagnosed in primary care settings, and 20% are incorrectly diagnosed with MDD. Given the substantial medical, economic and social costs involved with MDD, there is tremendous need for a simple objective biomarker test to aid clinicians in accurately identifying MDD. No test currently exists that can accurately diagnose MDD and distinguish it from other psychiatric conditions. Further, clinical response to antidepressant therapy requires as much as two months. There is enormous need for a test that can predict response within a few days of the inception of treatment. The potential market for an accurate diagnostic test for MDD is estimated at $5-8B annually. Payers of medical services would cover the cost of such a diagnostic test because accurately identifying and treating MDD would reduce the high medical costs arising from medical service delivery to patients with untreated depression, as well as improving outcomes for patients with comorbid medical conditions such as diabetes or heart disease. Another market for an MDD diagnostic test is pharmaceutical companies. These companies have uniformly retreated from discovery efforts in mood disorders, in part due to large- scale failure of numerous clinical trials. Part of the reason for these failures is the enrollment of inappropriate patients. An objective test of MDD could address this concern by providing certainty about the appropriateness of recruited subjects. The Pax Neuroscience diagnostic biomarker Gαs Sequestration Assay (GSA) indicates that MDD patients have a significantly greater proportion of Gαs captured in lipid rafts compared to non-depressed controls and can accurately identify patients suffering from MDD. Pax used the same principles that underpin the GSA to develop a C6 glioma (Gαs -GFP) FRAP assay which can reliably predict antidepressant efficacy. The proposed studies will convert that assay into high content screening (HCS) format, enabling an HCS campaign to find novel small molecules that target MDD. In addition we will develop a secondary screen using Neural Stem Cells, i n d u c e d from f i b r o b l a s t s o f d e p r e s s e d subjects with known responses to antidepressants (SSRIs), to confirm the efficacy of the screen. This secondary screen can be modified to evaluate treatment efficacy in MDD patients. This is an exciting proposal that offers an underlying technology that can both find new drugs and develop personalized therapy for depression.