Profiling neuroinflammatory markers and response to nusinersen in paediatric spinal muscular atrophy.

Humans Biomarkers / cerebrospinal fluid Female Male Oligonucleotides / therapeutic use Child, Preschool Cytokines / cerebrospinal fluid Infant Child Chemokine CCL4 / cerebrospinal fluid Chemokine CCL2 / cerebrospinal fluid Interleukin-8 / cerebrospinal fluid Neuroinflammatory Diseases / drug therapy Spinal Muscular Atrophies of Childhood / drug therapy Muscular Atrophy, Spinal / drug therapy Chemokine CCL11 / cerebrospinal fluid Vascular Endothelial Growth Factor A / cerebrospinal fluid
Biomarker CSF Neuroinflammation Nusinersen SMA

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
08 10 2024
Historique:
received: 25 07 2024
accepted: 25 09 2024
medline: 9 10 2024
pubmed: 9 10 2024
entrez: 8 10 2024
Statut: epublish

Résumé

Neuroinflammation is an emerging clinical feature in spinal muscular atrophy (SMA). Characterizing neuroinflammatory cytokines in cerebrospinal fluid (CSF) in SMA and their response to nusinersen is important for identifying new biomarkers and understanding the pathophysiology of SMA. We measured twenty-seven neuroinflammatory markers in CSF from twenty SMA children at different time points, and correlated the findings with motor function improvement. At baseline, MCP-1, IL-7 and IL-8 were significantly increased in SMA1 patients compared to SMA2, and were significantly correlated with disease severity. After six months of nusinersen treatment, CSF levels of eotaxin and MIP-1β were markedly reduced, while IL-2, IL-4 and VEGF-A were increased. The decreases in eotaxin and MIP-1β were associated with changes in motor scores in SMA1. We also detected a transient increase in MCP-1, MDC, MIP-1α, IL-12/IL-23p40 and IL-8 after the first or second injection of nusinersen, followed by a steady return to baseline levels within six months. Our study provides a detailed profile of neuroinflammatory markers in SMA CSF. Our data confirms the potential of MCP-1, eotaxin and MIP-1β as new neuroinflammatory biomarkers in SMA1 and indicates the presence of a subtle inflammatory response to nusinersen during the early phase of treatment.

Identifiants

DOI: 10.1038/s41598-024-74338-z PMID: 39379509
pubmed: 39379509
doi: 10.1038/s41598-024-74338-z
pii: 10.1038/s41598-024-74338-z
doi:

Substances chimiques

Biomarkers 0
nusinersen 5Z9SP3X666
Oligonucleotides 0
Cytokines 0
Chemokine CCL4 0
Chemokine CCL2 0
Interleukin-8 0
CCL2 protein, human 0
Chemokine CCL11 0
Vascular Endothelial Growth Factor A 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

23491

Subventions

Organisme : EU H2020-MSCA-ITN-2020
ID : SMABEYOND
Organisme : Medical Research Council
ID : MR/Y008405/1
Pays : United Kingdom

Informations de copyright

© 2024. The Author(s).

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Auteurs

Qiang Zhang (Q)

Genetics and Genomic Medicine Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.
School of Physical Education, Huangshan University, Huangshan, China.

Ying Hong (Y)

Infection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.

Chiara Brusa (C)

Developmental Neurosciences Research and Teaching Department, Great Ormond Street Institute of Child Health, The Dubowitz Neuromuscular Centre, University College London, London, UK.

Mariacristina Scoto (M)

Developmental Neurosciences Research and Teaching Department, Great Ormond Street Institute of Child Health, The Dubowitz Neuromuscular Centre, University College London, London, UK.

Nikki Cornell (N)

Developmental Neurosciences Research and Teaching Department, Great Ormond Street Institute of Child Health, The Dubowitz Neuromuscular Centre, University College London, London, UK.

Parth Patel (P)

Genetics and Genomic Medicine Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.

Giovanni Baranello (G)

Developmental Neurosciences Research and Teaching Department, Great Ormond Street Institute of Child Health, The Dubowitz Neuromuscular Centre, University College London, London, UK.
NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.

Francesco Muntoni (F)

Developmental Neurosciences Research and Teaching Department, Great Ormond Street Institute of Child Health, The Dubowitz Neuromuscular Centre, University College London, London, UK.
NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.

Haiyan Zhou (H)

Genetics and Genomic Medicine Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK. Haiyan.zhou@ucl.ac.uk.
NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK. Haiyan.zhou@ucl.ac.uk.

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questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Polynucléotides › Oligonucléotides › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Chimiokines › Protéines inflammatoires des macrophages › Chimiokine CCL4 › Profiling neuroinflammatory markers and...
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questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-8 › Profiling neuroinflammatory markers and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Maladies neuro-inflammatoires › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies neurodégénératives héréditaires › Amyotrophies spinales infantiles › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Maladies du système nerveux › Maladies neuromusculaires › Maladies du motoneurone › Amyotrophie spinale › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Chimiokines › Chimiokines CC › Chimiokine CCL11 › Profiling neuroinflammatory markers and...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines angiogéniques › Facteurs de croissance endothéliale vasculaire › Facteur de croissance endothéliale vasculaire de type A › Profiling neuroinflammatory markers and...