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Updated: May 28, 2026
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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-Treated SOD1-ALS: A Real-World Multicentre Cohort Study
Andrea Giordano1,2, Jessica Mandrioli3,4, Federica Cerri5
1Neurology 3-Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy.
International Journal of Molecular Sciences
|May 27, 2026
Summary
Tofersen treatment for SOD1-ALS shows decreased neurofilament light chain (NfL). Other biomarkers like GFAP, Tau, and UCHL-1 increased, suggesting multi-analyte profiling refines treatment response assessment beyond NfL alone.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Tofersen is a gene-targeted therapy for SOD1-ALS.
- Neurofilament light chain (NfL) is a biomarker for neurodegeneration, but may not fully reflect treatment response.
Purpose of the Study:
- To evaluate the longitudinal changes of multiple biomarkers in cerebrospinal fluid (CSF) and serum following tofersen treatment in SOD1-ALS patients.
- To assess if multi-analyte profiling offers a more comprehensive understanding of tofersen's biological effects compared to NfL alone.
Main Methods:
- Retrospective longitudinal study of 24 SOD1-ALS patients treated with intrathecal tofersen.
- CSF and serum biomarkers (NfL, GFAP, UCHL-1, Tau) were measured at baseline and follow-up visits using single-molecule array assays.
Main Results:
- CSF and serum NfL decreased after tofersen initiation, showing the clearest pharmacodynamic effect.
- CSF GFAP, Tau, and UCHL-1 increased progressively over time, as did serum GFAP, Tau, and UCHL-1.
- ALS Functional Rating Scale-Revised scores remained stable, and disease progression rate decreased.
- Greater NfL reduction was seen with pathogenic SOD1 variants; early NfL and UCHL-1 changes correlated with long-term disease progression.
Conclusions:
- Longitudinal multi-analyte biomarker profiling provides a more nuanced view of tofersen's biological response in SOD1-ALS.
- Combining NfL with GFAP, Tau, and UCHL-1 may improve the stratification of treatment response.
- These findings support the use of comprehensive biomarker panels in clinical trials and practice for SOD1-ALS.
