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Published on: March 4, 2014
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.
Background:
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. IsomiRs are microRNA (miRNA) isoforms that arise from alternative processing or editing events during miRNA biogenesis. While isomiRs may carry distinct biological and clinical relevance, their potential as cell-free biomarkers in neurodegeneration remains largely unexplored.
Methods:
Here, we investigated the prognostic utility of plasma isomiRs in ALS, using next-generation sequencing and two orthogonal statistical approaches.
Findings:
We profiled cell-free isomiRs in 154 ALS patients from a British cohort and identified higher levels of one isomiR, let-7g-5p.t, to be associated with longer survival. This finding was independently validated in an international ALS cohort of 200 patients. let-7g-5p.t prognostic utility was comparable to that of neurofilament light chain (NfL) or miR-181.
Conclusions:
These results establish isomiRs as a novel class of blood-based biomarkers in ALS with the potential to refine prognostication in clinical trials for neurodegenerative diseases.
Funding:
This study was funded by Target ALS the Israel Science Foundation (3497/21, 424/22) and the CReATe Consortium. All additional funding can be found under the Acknowledgments.
Insights
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.
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.
