Neuronal Pentraxin 2 as a Potential Biomarker for Nusinersen Therapy Response in Adults with Spinal Muscular Atrophy: A Pilot Study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40868076", "kind": "science-record", "revision": 3, "content_hash": "sha256:1ec3c0ecd9dbbf351bfbdf8200791464bc99c6c35e3f381d37cb72bd8127c4ab", "created_at": "2026-11-01T20:30:59Z", "updated_at": "2026-11-01T22:14:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Neuronal Pentraxin 2 as a Potential Biomarker for Nusinersen Therapy Response in Adults with Spinal Muscular Atrophy: A Pilot Study.", "doi": "10.3390/biomedicines13081821", "pmid": "40868076", "authors": ["Svenja Neuhoff", "Linda-Isabell Schmitt", "Kai Christine Liebig", "Stefanie Hezel", "Nick Isana Tilahun", "Christoph Kleinschnitz", "Markus Leo", "Tim Hagenacker"], "journal": "Biomedicines", "year": 2025, "abstract": "Background: The treatment landscape for spinal muscular atrophy (SMA) has changed significantly with the approval of gene-based therapies such as nusinersen for adults with SMA (pwSMA). Despite their efficacy, high costs and treatment burden highlight the need for biomarkers to objectify or predict treatment response. This study aimed to identify such biomarkers. Methods: A proteomic analysis of cerebrospinal fluid (CSF) from pwSMA (n = 7), who either significantly improved (SMA Improvers) or did not improve in motor function (SMA Non-Improvers) under nusinersen therapy, was performed. Data are available via ProteomeXchange with identifier PXD065345. Candidate biomarkers-Neuronal Pentraxin 2 (NPTX2), Contactin 5 (CNTN5), and Anthrax Toxin Receptor 1 (ANTXR1)-were investigated by ELISA in serum and CSF from an independent pwSMA cohort (n = 14) at baseline, 2 and 14 months after therapy initiation. Biomarker concentrations were correlated with clinical outcomes. Additionally, NPTX2 was stained in spinal cord sections from a mild SMA mouse model (FVB.Cg-Smn1tm1Hung Tg(SMN2)2Hung/J). Results: CSF NPTX2 levels decreased in pwSMA after 14 months of nusinersen therapy, independent of clinical response. The change in NPTX2 serum levels over 14 months of nusinersen treatment correlated with the change in HFMSE during this period. CNTN5 and ANTXR1 showed no significant changes. In the SMA mouse model, NPTX2 immunoreactivity increased at motoneuron loss onset. Conclusions: NPTX2 emerges as a potential biomarker of treatment response to nusinersen in pwSMA suggesting its significant pathophysiological role in late-onset SMA, warranting further investigation.", "claims": [{"id": "claim-method", "statement": "Correlations between the protein levels and motor scores HFMSE and RULM were calculated using Spearman’s rank correlation coefficient.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40868076", "locator": "sections[10] \"2.8. Statistical Analysis\" paragraph 3", "quote": "Correlations between the protein levels and motor scores HFMSE and RULM were calculated using Spearman’s rank correlation coefficient."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The protein ratios between the groups obtained from the proteomic analysis are available as a Supplementary Online Resource (Table S1). The mass spectrometry proteomics data have been deposited to the Proteo-meXchange Consortium via the PRIDE partner repository with the dataset identifier PXD065345. The other datasets generated and analyzed during the current study are not publicly available due to the inclusion of clinical patient data that cannot be disclosed for data protection and privacy reasons but are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40868076", "locator": "sections[23] \"notes\" paragraph 1", "quote": "The protein ratios between the groups obtained from the proteomic analysis are available as a Supplementary Online Resource (Table S1). The mass spectrometry proteomics data have been deposited to the Proteo-meXchange Consortium via the PRIDE partner repository with the dataset identifier PXD065345. The other datasets generated and analyzed during the current study are not publicly available due to the inclusion of clinical patient data that cannot be disclosed for data protection and privacy reasons but are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Changes in the NPTX2 serum level from T0 to T2 correlated negatively with changes in the HFMSE from T0 to T2 (r = −0.688, p = 0.019, n = 11) across all pwSMA.", "kind": "quantitative", "target": {"value": 0.019, "unit": "p-value", "tolerance": null, "source": "Changes in the NPTX2 serum level from T0 to T2 correlated negatively with changes in the HFMSE from T0 to T2 (r = −0.688, p = 0.019, n = 11) across all pwSMA (Figure 4)."}, "evidence": [{"asset": "source:pmid:40868076", "locator": "sections[13] \"3.2. ELISA-Based Quantification of NPTX2, CNTN5, and ANXTR1 in CSF and Serum\" paragraph 3", "quote": "Changes in the NPTX2 serum level from T0 to T2 correlated negatively with changes in the HFMSE from T0 to T2 (r = −0.688, p = 0.019, n = 11) across all pwSMA (Figure 4)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Changes in the NPTX2 serum level from T0 to T2 correlated negatively with changes in the HFMSE from T0 to T2 (r = −0.688, p = 0.019, n = 11) across all pwSMA.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40868076"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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