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

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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.