Neuronal Screening Platform for Improved Mental Healthcare (NSP-4-IMH)

**挑战：**严重的精神疾病（SMI），如精神分裂症，会给患者带来巨大的痛苦。这对个人（精神分裂症患者的预期寿命减少10-25年）和社会造成了巨大的成本负担，损失了工作日和护理费用。需要新的药物来改善重度精神分裂症患者的预后；然而，我们无法确定最佳候选药物是一个重大挑战，因为它经常导致临床试验失败，成本高昂；从而降低了对药物开发投资的兴趣（精神病学临床试验的成本在1000万美元到1亿多美元之间）。**答案在于使用人体细胞进行安全、经济的实验室筛选：在涉及单个人体参与者或进行繁琐的临床试验程序之前，有效地剔除不起作用的化合物，并确定成功率最高的化合物。作为一项可行性研究，我们选择专注于精神分裂症；此外，这种人类细胞方法可以扩展到许多其他精神健康障碍。**创新：**我们将使用从50名精神分裂症患者的血液样本中提取的细胞，并使用分子方法将其转化为脑细胞（神经元）。我们的平台将使用数千个微型电极来测量这些细胞的活动；这就好像我们在检查50个不同的人的反应——但都是在实验室里的一个循环中完成的。由于精神分裂症患者细胞的活性与正常人细胞的活性不同，因此该平台可用于测试不同化合物的效果——技术人员在非典型细胞中寻找恢复的迹象，这表明一种可能进入临床试验的药物。在未来，这种方法还将使医生能够选择哪些患者对某种治疗反应最好。**价值：**提高识别最佳药物用于试验的能力将使公司在商业上受益，并增加开发新的成功治疗重度精神障碍的可能性。我们将利用50名精神分裂症患者的细胞系开发首个商业化筛选平台。据估计，仅在英国，精神分裂症的直接和间接费用每年就超过70亿英镑，因此这是一个重要的起点。该平台将是第一个此类平台，为更有效和高效的精神药物开发开辟道路。

**The Challenge:** Severe mental illnesses (SMI), such as schizophrenia, causes immense suffering to those who experience it. It presents a significant cost burden, both for individuals (those experiencing schizophrenia have a reduced life expectancy of 10-25 years) and society, through lost workdays and care costs.New medications are needed to improve the outcomes for people experiencing SMI; however, our inability to identify the best candidate drugs presents a significant challenge, as it often results in failed clinical trials, at significant cost; in turn reducing appetite for investment in drug development (clinical trials in psychiatry cost between $10m to over $100m).**How?** The answer lies in safe, cost-effective lab-based screening using human cells: efficiently weeding out the compounds that don't work and identifying the ones with the highest chance of success, before involving a single human participant or engaging burdensome clinical trial procedures. As a feasibility study, we have chosen to focus on schizophrenia; furthermore, this human cellular approach can be expanded to work for many other mental health disorders.**The Innovation:** We will use cells derived from blood samples taken from 50 patients with schizophrenia and use molecular methods to turn these into brain cells (neurons). Our platform will use thousands of miniature electrodes to measure the activity in these cells; it will be as if we were examining 50 different people's reactions -- but all done in a single cycle, in the laboratory.Because the activity is different in cells from people with schizophrenia compared to cells from people without, the platform can be used to test the effect of different compounds -- with technicians looking for signs of recovery in the atypical cells, signalling a likely drug to progress to clinical trial. In the future this approach will also enable is to select which patients will respond best to a given therapy.**The Value:** Improving the ability to identify the best drugs to take to trial will both benefit companies commercially and increase the likelihood of developing new successful treatments for SMI.We will develop the first commercial screening platform with cell lines from 50 schizophrenia patients. The direct and indirect costs of schizophrenia are estimated at over £7 billion per year, in the UK alone, so this is an important starting point The platform will be the first of its kind and severe mental illness open the route to more effective and efficient psychiatric drug development.