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Publication Detail
Circulating miR-181a-5p is a prognostic biomarker for amyotrophic lateral sclerosis
  • Publication Type:
    Working discussion paper
  • Authors:
    Magen I, Coenen-Stass A, Yacovzada N, Grosskreutz J, Lu C-H, Greensmith L, Malaspina A, Fratta P, Hornstein E
  • Publication date:
  • Status:
Abstract Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease affecting the motor neuron system. Variability in the rate of disease progression has limited the effectiveness of ALS clinical trials. Thus, better outcome measures are 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 apply an unbiased high-throughput approach to define miRNA levels in a large cohort of ALS patients. Crucially, we conduct our analysis also on longitudinal samples reflecting disease progression, and are able to integrate detailed clinical phenotyping in our analysis. We find miR-181a-5p levels to be stable throughout the 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 (×8) difference in miR-181a-5p levels between the two prognosis subgroups was robustly measurable by quantitative real time PCR. In conclusion, miR-181a-5p plasma levels can predict disease course in ALS, identifying it as a novel biomarker for patient stratification with the potential to greatly enhance the effectiveness of clinical trials. One Sentence Summary higher plasma miR-181a-5p levels increase mortality risk in ALS patients.
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