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Published on: March 4, 2014
IsomiR Utility in Amyotrophic Lateral Sclerosis Prognostication
Yahel Cohen1,2, Ilan Sinai1,2, Iddo Magen1,2
1Department ofMolecular Genetics, 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.
Method:
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.
Conclusion:
These results establish isomiRs as a novel class of blood-based biomarkers in ALS with potential to refine prognostication in clinical trials for neurodegenerative diseases.
Funding:
Target ALS, Israel Science Foundation (ISF 3497/21, 424/22) and the CReATe Consortium. All additional funding can be found in the Acknowledgements section of this paper.
Insights
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.
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.
