Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) define two ends of a spectrumof clinically, genetically, and mechanistically related neurodegenerative diseases. Due to symptom overlaps withother diseases, the early and accurate diagnosis of ALS and FTD is challenging. This leads to delayedintervention and stands as a major barrier to the efficient clinical testing of new disease-modifying therapeutics.Efforts to develop new therapies and apply them early would be greatly facilitated by biomarkers that reveal thestate of ALS/FTD pathogenesis in vivo at the molecular level. Currently there are no objective diagnostics tonon-invasively detect and measure the most defining molecular feature of ALS/FTD pathogenesis: accumulationof deposits of the TAR DNA-binding protein 43 (TDP43). A buildup of TDP43 deposits occurs in ~97% of ALSand ~50% of FTD cases and is thought to be a central driver of disease pathogenesis. This proposal will generateproof of concept for an affordable, accessible and innovative approach to detect and quantify TDP43 pathologyin ALS/FTD human eyes using patent protected small molecule fluorescent retinal contrast agents.
Public Health Relevance Statement: Project Narrative
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease defined by the presence of TPD43
inclusions. The proposed research aims to establish the presence of TDP43 deposits in the retina of human
cadaver eyes to validate the development of a non-invasive diagnostic test through the eye.
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