ArticleScientific reports2025
Neurodegenerative and neuroinflammatory changes in SOD1-ALS patients receiving tofersen.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Safety profile of tofersen in amyotrophic lateral sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- SOD1 co-pathologies in the brain: insights from neuropathological evidence and implications.Acta neuropathologica · 2026Review
- Acyclic artificial nucleic acid substitution expands the safe design space of gapmer ASOs by preventing P54nrb mislocalization.NAR molecular medicine · 2026Article
- Beyond Coding Variants: RNA-Level Mechanisms in Human Disease and Precision Therapeutics.Genes · 2026Review
- Serum neurofilaments for motoneuron and dementia diseases: a German multicenter cohort study.Journal of neurology · 2026Article
- High Prevalence of SOD1 Pathogenic Variants in the UK Biobank: Implications for Early Intervention in Amyotrophic Lateral Sclerosis.Annals of neurology · 2026Article
- Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-TreatedInternational journal of molecular sciences · 2026Article
- Elimination of senescent cells fails to attenuate disease progression in an ALS mouse model.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Central nervous system concentrations of nano- and microplastics and risk of amyotrophic lateral sclerosis.Brain communications · 2026Article
- Neurocritical progression in amyotrophic lateral sclerosis: pathological relevance and validation.Open life sciences · 2026Review
- Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications.Molecular therapy. Nucleic acids · 2025Article
- Targeted Proteomics upon Treatment with Tofersen Identifies Novel Response Markers for Superoxide Dismutase 1-Linked Amyotrophic Lateral Sclerosis.Annals of neurology · 2025Article
- Modulating Cerebrospinal Fluid Composition in Neurodegenerative Processes: Modern Drug Delivery and Clearance Strategies.International journal of molecular sciences · 2025Review
- Paper-Based Electrochemical Device Modified with Palladium: Sensor for the Detection of Serotonin and an Immunosensor for the Detection of SOD1.ACS omega · 2025Article
- Concurrent nanotherapeutics and regulatory updates for the management of amyotrophic lateral sclerosis: a focused review for orphan drug (Tofersen).Orphanet journal of rare diseases · 2025Review
- Methotrexate therapy as a promising long-term treatment approach for immune-mediated adverse reactions of tofersen in SOD1-ALS: a case report.Journal of neurology · 2025Article
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12 authors.
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Abstract
The initiation of tofersen, a new specific antisense oligonucleotide (ASO) for SOD1 pathology, marked a significant turning point for SOD1-ALS patients. While clinical trials and early access program studies reported a significant reduction in plasma and cerebrospinal fluid (CSF) neurofilament levels, neuroinflammation following prolonged treatment was never assessed. In this multicenter study, we evaluated a cohort of 18 SOD1-ALS patients treated with tofersen, analyzing correlations between biomarkers of neurodegeneration/neuroinflammation and clinical variables indicative of disease progression. NfL, NfH, CHI3L1, and Serpina1 levels in serum and CSF were determined by semi-automated immunoassays (Ella™ technology). Generalized linear mixed models were employed to investigate longitudinal trends of these biomarkers. Our data highlighted a progressive decrease in CSF neurofilament levels during tofersen treatment (MR = 0.97, 95% CI 0.94-0.99, p = 0.006 and MR = 0.98, 95% CI 0.95-1.00, p = 0.076 for NfL and NfH in CSF, respectively). Conversely, CSF levels of SerpinA1 and CHI3L1 increased over time (MR = 1.12, 95% CI 1.08-1.16, p < 0.0001 and MR = 1.039, 95% CI 1.015-1.062, p = 0.001 for SerpinA1 and CHI3L1 in CSF, respectively), but these modifications were most apparent after six and twelve months of therapy, respectively. Disease progression rate did not correlate with these biomarker trends. We observed a significant decrease in neurofilament levels during Tofersen treatment, alongside an increase in neuroinflammatory markers, potentially linked to an immune response triggered by ASO treatment. Given the limited data on tofersen's long-term efficacy in ALS due to its recent introduction, identifying biomarkers that predict clinical outcomes such as diminished therapeutic response or adverse effects is crucial. These biomarkers may help to better understand the underlying pathomechanisms of ALS and tofersen's role in modulating disease progression.
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