Michael Ward, MD, PhD
National Institutes of Health
Proteogenomic identification of TDP-43-related splicing dysfunction in ALS/FTD
A major impediment to clinical trials of potentially disease-modifying therapies for ALS has been the lack has been a lack of robust biomarkers of disease-relevant neuronal dysfunction. Loss of function of TDP-43 is now recognized as an early and defining pathologic event in most forms of ALS, and causes abnormal RNA splicing in neurons. Through coordinated studies in human iPSC neurons, ALS patient brain and cerebrospinal fluid samples, we aim to develop novel protein-based biomarkers of RNA mis-splicing in ALS patients with TDP-43 pathology.