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Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis
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IsomiR utility in amyotrophic lateral sclerosis prognostication.

Yahel Cohen1, Ilan Sinai1, Iddo Magen1

  • 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.

Med (New York, N.Y.)
|November 22, 2025
PubMed
Summary

Plasma isomiRs, specifically let-7g-5p.t, show prognostic utility in amyotrophic lateral sclerosis (ALS). Higher levels correlate with longer survival, offering new potential for ALS biomarker discovery.

Keywords:
amyotrophic lateral sclerosisisomiRsmachine learning in biomedicinemiRNAneurodegenerative diseasesprognostic biomarkerssmall RNA biomarkerssurvival analysistranslation to patientstranslational neuroscience

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Area of Science:

  • Neuroscience
  • Genetics
  • Biomarker Discovery

Background:

  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by motor neuron loss.
  • IsomiRs, miRNA variants from alternative processing, have unexplored potential as cell-free biomarkers.

Purpose of the Study:

  • To investigate the prognostic value of plasma isomiRs in ALS patients.
  • To explore isomiRs as novel blood-based biomarkers for neurodegenerative diseases.

Main Methods:

  • Next-generation sequencing was used to profile cell-free isomiRs in ALS patient plasma.
  • Two orthogonal statistical approaches were employed for analysis.

Main Results:

  • Elevated levels of the isomiR let-7g-5p.t were associated with longer survival in ALS patients.
  • This finding was validated in an independent international cohort.
  • The prognostic utility of let-7g-5p.t was comparable to established biomarkers like NfL.

Conclusions:

  • IsomiRs represent a new class of blood-based biomarkers for ALS.
  • These findings can potentially enhance prognostication in clinical trials for neurodegenerative diseases.