I-Corps: Drug discovery pathway for neural cells

这个i-Corps项目的更广泛的影响/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的新疗法的临床成功的可能性。该项目预计将在2022年将更多的化合物带入临床前阶段，并在2025年将化合物转移到临床阶段。除了新疗法的开发，我们技术的更广泛影响是我们的药物发现平台将导致范式的变化。如果我们的方法成功地发现了具有高临床疗效的化合物，许多药物开发商将从细胞系转向使用临床相关的原代细胞培养，从而导致我们的技术的价值增加，因为在有效的专利窗口期间，需要在成人神经细胞中进行筛选。I-Corps项目基于开发一种新的筛选系统，这是第一个在成人神经细胞中直接测试化合物的系统。目前的神经筛查使用胚胎或新生神经细胞，这导致了非常高的临床失败率，因为这些细胞不能代表那些患有神经疾病和障碍的人的目标成人神经群体。建议的新型筛选系统可以持续提供数以百万计的高纯度和高活性的神经细胞，以取代胚胎/新生神经细胞直接在成人神经细胞中进行药物筛选。这种新的成人神经细胞筛选系统的好处是：1)减少了阳性结果在临床前阶段无效的机会；2)增加了发现年龄/性别特定化合物的几率；3)能够找到成人神经细胞特有的新化合物/靶点；4)降低了药物开发的总成本。我们正在使用这项技术来发现可以治疗神经退行性疾病和神经创伤的新型药物/化合物/靶点。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.