Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis [article]

Iddo Magen, Anna Maria Laura Coenen-Stass, Nancy S Yacovzada, Julian Grosskreutz, Ching-Hua Lu, Linda Greensmith, Andrea Malaspina, Pietro Fratta, Eran Hornstein
2019 bioRxiv   pre-print
Amyotrophic lateral sclerosis (ALS) is a ruthless neurodegenerative disease affecting the motor neuron system. Variability of disease progression and lack of refined readouts have limited the effectiveness of ALS clinical trials, making novel tools for patient stratification at trial recruitment, and better outcome measures, desperately needed in order to achieve therapeutic progress. Here, we investigate the potential of plasma cell-free microRNAs as biomarkers to predict ALS progression. We
more » ... ply an unbiased high-throughput approach to define miRNA levels in a large cohort of ALS patients and controls. Crucially, we conduct our analysis also on longitudinal samples reflecting disease progression, and are able to integrate detailed clinical phenotyping in our analysis. We identify miR-181a-5p levels to be stable during disease course and demonstrate that high miR-181a-5p plasma levels predict shortened survival in ALS patients, with a 2.5 fold reduction in median survival for patients with high miR-181a-5p plasma levels. We replicated this finding in an independent validation cohort, where an eight-fold (X8) difference in miR-181a-5p levels between the two prognosis subgroups was robustly measurable by quantitative real time PCR. In conclusion, miR-181 plasma levels can predict disease course in ALS suggesting it as a novel biomarker for patient stratification that might will greatly enhance the effectiveness of clinical trials.
doi:10.1101/833079 fatcat:tggw24atvrgqpkooyxcko2wtla