I-Corps: Drug discovery pathway for neural cells

I-Corps项目更广泛的影响/商业潜力是开发新技术，以增加使用我们的新筛查系统开发神经退行性疾病和神经创伤新疗法的临床成功概率。该项目预计将在2022年将更多化合物带入临床前阶段，并在2025年将化合物推向临床阶段。除了新疗法的开发，我们的技术更广泛的影响是我们的药物发现平台将导致范式的改变。如果我们的方法成功地发现具有高临床疗效的化合物，许多药物开发人员将从细胞系转向使用临床相关的原代细胞培养，从而增加我们技术的价值，因为在有效的专利窗口期间，将需要在成人神经细胞中进行筛选。这个I-Corps项目是基于一种新型筛选系统的开发，这是同类系统中的第一个，可以直接在成人神经细胞中测试化合物。目前的神经筛查使用胚胎或新生儿神经细胞，这导致很高的临床失败率，因为这些细胞不能代表患有神经系统疾病和障碍的目标成人神经群体。所提出的新型筛选系统可以持续提供数千万个高纯度和高活力的神经细胞，直接在成人神经细胞中代替胚胎/新生儿神经细胞进行药物筛选。这种新的成人神经细胞筛选系统的好处是：1)减少了阳性反应在临床前阶段无效的机会；2)发现年龄/性别特异性化合物的几率增加；3)发现成体神经细胞特有的新化合物/靶点的能力；4)降低了药物开发的总成本。我们正在利用这项技术发现可以治疗神经退行性疾病和神经创伤的新药/化合物/靶点。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of novel technology to increase the probability of clinical success in developing novel therapeutics for neurodegenerative disorders and neurotrauma using our novel screening system. This project is expected to bring several more compounds to the preclinical stages in 2022 and move compounds into the clinical stages by 2025. The broader impact of our technology beyond the development of novel therapeutics is the change in paradigm our drug discovery platform will cause. If our method is successful in discovering compounds with high clinical efficacy, many drug developers will switch from cell lines to using clinically relevant primary cell cultures, resulting in an increase in the value of our technology as it will be needed during the active patent window to conduct screenings in adult neural cells.This I-Corps project is based on the development of a novel screening system, the first of its kind, to test compounds directly in adult neural cells. Current neural screens use embryonic or newborn neural cells which leads to a very high clinical failure rate as those cells do not represent the target adult neural population in those with neurological diseases and disorders. The proposed novel screening system can consistently provide 10s of millions of neural cells of high purity and viability to conduct drug screenings directly in adult neural cells in place of embryonic/newborn neural cells. The benefits of this novel screening system in adult neural cells are 1) reduced chances of positive hits not being effective at pre-clinical stages; 2) increased odds of finding age/sex specific compounds; 3) ability to find novel compounds/targets unique to adult neural cells; 4) reduced overall cost of drug development. We are using this technology to discover novel drugs/compounds/targets that can treat neurodegenerative diseases and neurotrauma.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.