Observational studyOrphanet journal of rare diseases2021
Increased chitotriosidase 1 concentration following nusinersen treatment in spinal muscular atrophy.
Observational study in Orphanet journal of rare diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Effectiveness and Safety of Nusinersen and Risdiplam in Spinal Muscular Atrophy: A Systematic Review.Annals of clinical and translational neurology · 2026Pooled it
- Serum circulating cell-free messenger RNA profile response to risdiplam treatment in adult patients with late-onset spinal muscular atrophy.Brain communications · 2026Article
- Application of Biomarkers in Spinal Muscular Atrophy.International journal of molecular sciences · 2025Review
- Neurodegenerative and neuroinflammatory changes in SOD1-ALS patients receiving tofersen.Scientific reports · 2025Article
- Cell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment.Nature communications · 2024Article
- Macrophage inclusions in cerebrospinal fluid following treatment initiation with antisense oligonucleotide therapies in motor neuron diseases.Neurological research and practice · 2024Article
- Biomarkers in 5q-associated spinal muscular atrophy-a narrative review.Journal of neurology · 2023Review
- Molecular Biomarkers for the Diagnosis, Prognosis, and Pharmacodynamics of Spinal Muscular Atrophy.Journal of clinical medicine · 2023Review
- Cerebrospinal fluid characteristics of patients treated with intrathecal nusinersen for spinal muscular atrophy.Muscle & nerve · 2022Article
- Comprehensive Serum Proteome Profiling of Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome Patients with B-Cell ALL Receiving CAR T19.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Glial fibrillary acidic protein in cerebrospinal fluid of patients with spinal muscular atrophy.Annals of clinical and translational neurology · 2022Article
- Biochemical and clinical biomarkers in adult SMA 3-4 patients treated with nusinersen for 22 months.Annals of clinical and translational neurology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStudies regarding the impact of (neuro)inflammation and inflammatory response following repetitive, intrathecally administered antisense oligonucleotides (ASO) in 5q-associated spinal muscular atrophy (SMA) are sparse. Increased risk of hydrocephalus in untreated SMA patients and a marginal but significant increase of the serum/CSF albumin ratio (Qalb) with rare cases of communicating hydrocephalus during nusinersen treatment were reported, which confirms the unmet need of an inflammatory biomarker in SMA. The aim of this study was to investigate the (neuro)inflammatory marker chitotriosidase 1 (CHIT1) in SMA patients before and following the treatment with the ASO nusinersen.
methodsIn this prospective, multicenter observational study, we studied CSF CHIT1 concentrations in 58 adult and 21 pediatric patients with SMA type 1, 2 or 3 before treatment initiation in comparison to age- and sex-matched controls and investigated its dynamics during nusinersen treatment. Concurrently, motor performance and disease severity were assessed.
resultsCHIT1 concentrations were elevated in treatment-naïve SMA patients as compared to controls, but less pronounced than described for other neurodegenerative diseases such as amyotrophic lateral sclerosis. CHIT1 concentration did not correlate with disease severity and did not distinguish between clinical subtypes. CHIT1 concentration did show a significant increase during nusinersen treatment that was unrelated to the clinical response to nusinersen therapy.
conclusionsCHIT1 elevation in treatment-naïve SMA patients indicates the involvement of (neuro)inflammation in SMA. The lacking correlation of CHIT1 concentration with disease severity argues against its use as a marker of disease progression. The observed CHIT1 increase during nusinersen treatment may indicate an immune response-like, off-target reaction. Since antisense oligonucleotides are an establishing approach in the treatment of neurodegenerative diseases, this observation needs to be further evaluated.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.