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IsomiR Utility in Amyotrophic Lateral Sclerosis Prognostication.

Yahel Cohen1,2, Ilan Sinai1,2, Iddo Magen1,2

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Medrxiv : the Preprint Server for Health Sciences
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Summary
This summary is machine-generated.

Plasma isomiRs show prognostic utility in Amyotrophic Lateral Sclerosis (ALS). Higher levels of a specific isomiR, let-7g-5p.t, correlate with longer survival in ALS patients, offering new biomarker potential.

Keywords:
Amyotrophic Lateral SclerosisPrognostic biomarkersisomiRsmachine learning in biomedicinemiRNAneurodegenerative diseasessmall RNA biomarkerssurvival analysistranslational neuroscience

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Area of Science:

  • Neuroscience
  • Genomics
  • Biomarker Discovery

Background:

  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by motor neuron loss.
  • IsomiRs, variants of microRNAs (miRNAs), have unexplored potential as cell-free biomarkers in neurodegeneration.
  • Current understanding of isomiR roles in neurodegenerative diseases is limited.

Purpose of the Study:

  • To investigate the prognostic value of plasma isomiRs in Amyotrophic Lateral Sclerosis (ALS).
  • To explore isomiRs as novel blood-based biomarkers for ALS prognostication.
  • To assess the clinical relevance of isomiRs in neurodegenerative disease research.

Main Methods:

  • Next-generation sequencing was employed to profile cell-free isomiRs in plasma.
  • Two orthogonal statistical approaches were utilized for data analysis.
  • The study involved a British cohort of 154 ALS patients and an international validation cohort of 200 patients.

Main Results:

  • Higher levels of the isomiR let-7g-5p.t were associated with longer survival in ALS patients.
  • This finding was independently validated in a separate international cohort.
  • The prognostic utility of let-7g-5p.t was comparable to established biomarkers like neurofilament light chain (NfL) and miR-181.

Conclusions:

  • IsomiRs represent a novel class of blood-based biomarkers for ALS.
  • Plasma isomiRs can potentially refine prognostication in clinical trials for neurodegenerative diseases.
  • This study highlights the significance of isomiRs in understanding ALS progression and patient outcomes.