The ASPIRE Path in Molecular Medicine

Frontotemporal dementia (FTD) is a group of dementias linked by changes in behavior and language that frequently co-occurs with amyotrophic lateral sclerosis (ALS).1 With no disease-specific biomarkers, these heterogeneous diseases are plagued by misdiagnosis and diagnostic delay, affecting patient wellbeing and reducing statistical power in research, ultimately hindering attempts to cure them.2 We propose a systematic approach to developing a phenotypic profile of FTD and ALS patients in Vanderbilt’s Synthetic Derivative, including imaging and diagnostic codes, which will help identify undiagnosed cases. This information can be used both to increase statistical power for human genetic analyses in BioVU, which may fuel an understanding of the biology underlying these diseases and help to identify additional risk factors contributing to them. By participating in APMM I will gain the expertise, resources, and structure to expand this project from a tool to identify cases for genetic analyses to a resource for clinicians, flagging individuals for additional screening for FTD or ALS. In addition to providing another use case for our tool, clinical mentorship will directly contribute to the development of the tool itself through my clinical mentor’s input, I will better understand key factors in clinical care and diagnostics.

Citations: 1. Katzeff JS, Bright F, Phan K, et al. Biomarker discovery and development for frontotemporal dementia and amyotrophic lateral sclerosis. Brain J Neurol. 2022;145(5):1598-1609. doi:10.1093/brain/awac077  2. Goutman SA, Hardiman O, Al-Chalabi A, et al. Recent advances in the diagnosis and prognosis of ALS. Lancet Neurol. 2022;21(5):480-493. doi:10.1016/S1474-4422(21)00465-8