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Presymptomatic detection and XJB 1-5-131 treatment efficacy in Huntington disease models

Although some neurodegenerative diseases can be identified by behavioral characteristics relatively late in disease progression, we currently lack methods to predict who has developed disease before the onset of symptoms, when onset will occur, or the outcome of therapeutics. New biomarkers are needed. Here we describe spectral phenotyping, a new kind of biomarker that makes disease predictions based on chemical rather than biological endpoints in cells. Spectral phenotyping uses Fourier transform infrared (FTIR) spectromicroscopy to produce an absorbance signature which predicts disease class with high probability in the absence of overt symptoms. Moreover, FTIR chemical signatures accurately predicts neurodegenerative disease using cells as surrogate cells. The FTIR chemical signatures provide a fingerprint for following drug efficacy of XJB-5-131, a powerful antioxidant that is targeted to mitochondria. Our results suggest a mechanism to detect, classify disease, and monitor both disease progression and its reversal by therapeutic agents.

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