I-Corps: Novel diagnostic tool and compound repurposing for early detection and alleviation of Alzheimer's disease

这个I-Corps项目的更广泛的影响/商业潜力与美国阿尔茨海默病（AD）日益增加的患病率有关，而没有实际有效的药物。作为美国第三大死亡原因，每年用于治疗/护理AD患者的医疗保健支出接近3000亿美元。据估计，到2060年，AD和其他形式的痴呆症患者人数将增加到1390万。AD患者的生活质量受到记忆丧失的严重影响，使他们依赖辅助生活。开发新的药理学策略，可以有效地减轻AD的病理和减轻症状，将是非常有益的患者和照顾者。此外，鉴于AD与其他神经退行性疾病（如帕金森病和自闭症）和其他流行疾病（如2型糖尿病）具有相似的病理生理异常，所提出的化合物可能广泛用于单独治疗这些不同的疾病或与目前现有的疗法联合治疗。考虑到人类平均寿命的增加以及患有AD和其他神经退行性疾病的老年人数量的同时增加，我们预计用于治疗许多神经退行性疾病的潜在数十亿美元市场。该I-Corps项目旨在验证可能减缓AD进展的一类化合物的客户细分和产品市场适合性。初步数据表明，AD患者和AD动物模型血液中的某些氨基酸（BCAA）升高，因为它们在体内不能有效分解。由于支链氨基酸可导致神经元损伤和神经信使失衡，可能导致AD的发展，因此可以控制支链氨基酸循环水平的药物成为有吸引力的目标。拟议的I-Corps技术是重新利用一类已显示降低BCAA水平的现有化合物，以治疗AD病理和症状。这些化合物与目前的AD药物相比具有不同的作用机制，这些药物未能显示出任何有意义的记忆功能改善，因此使它们非常新颖，并且很有可能成功治疗AD。通过开发/精炼这些化合物并测试其功效和安全性，I-Corps计划之后的工作将成为真正的转化研究，并为人类产生关键产品。该奖项反映了NSF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 relates to the ever-increasing prevalence of Alzheimer's disease (AD) in the US without a drug that actually works. Being the third leading cause of mortality in the US, the annual healthcare expenditure for treating/care individuals with AD is nearly $300 billion. It is estimated that the number of people with AD and other forms of dementia will grow to 13.9 million by 2060. The quality of life of AD patients is severely impacted by memory loss that makes them rely on assisted living. Development of new pharmacological strategy that can effectively alleviate AD pathology and reduce symptoms will be very beneficial for the patients and caregivers. Moreover, given that AD shares similar pathophysiological abnormalities with other neurodegenerative diseases such as Parkinson's disease and autism, and other prevalent disorders such as Type 2 diabetes, the proposed compounds may potentially be broadly used for treating these different disorders alone or in conjunction with current existing therapies. Considering the increasing average lifespan of humans and the concurrent increase in the number of older individuals with AD and other neurodegenerative disorders, we anticipate a potential multi-billion dollar market for treatment of a number of neurodegenerative diseases. This I-Corps project seeks to validate the customer segments and product-market fit for a class of compounds that may slow down the progression of AD. The preliminary data demonstrate that certain amino acids (BCAAs) in blood of AD patients and an animal model of AD are elevated because they are not efficiently broken down in the body. Since BCAAs can cause neuronal damage and imbalance of neural messengers that may lead to development of AD, drugs that can control circulating levels of BCAAs become attractive targets. The proposed I-Corps technology is to repurpose a class of existing compounds that have shown to lower BCAA levels in order to treat AD pathology and symptoms. These compounds have a different mechanism of action compared to current AD drugs that have failed at showing any meaningful improvement in memory function, thus making them very novel and highly likely to succeed at treating AD. By developing/refining these compounds and testing its efficacy and safety, the work following the I-Corps program will become a truly translational research and generate a critical product for the humanity.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.