PXD054900

PXD054900 is an original dataset announced via ProteomeXchange.

Title	Longitudinal Proteomic Fingerprinting in CSF of Nusinersen-Treated Patients with 5q-Associated Spinal Muscular Atrophy
Description	Abstract Introduction: 5q-associated spinal muscular atrophy (SMA) is a motor neuron disease causing progressive alpha motor neuron degeneration, muscle atrophy, and weakness. Intrathecal therapy with the antisense oligonucleotide Nusinersen modifies the disease course. However, biomarkers for understanding underlying molecular pathomechanisms and monitoring therapy are not yet known. Methods: 130 cerebrospinal fluid (CSF) samples from 24 SMA type 2 and 3 adult patients were collected over 3.5 years and CSF proteome was using mass spectrometry (MS). By employing two complementary MS protein quantification methods, label-free quantification (LFQ) and tandem mass tag (TMT) isotopic labeling, specific protein patterns reflecting changes in the CSF in the context of nusinersen therapy were identified. These results were combined with cellular and metabolic profiles. Results: Nusinersen therapy led to a median motor function improvement of 2.2 Hammersmith Functional Motor Scale Expanded points after 10 months and 2.6 points after 34 months. Albumin concentration and albumin quotient (CSF/serum) increased, as did the number of macrophages in the CSF under nusinersen therapy. Albumin, glucose, and lactate concentrations were inversely correlated with clinical improvement. MS analysis of CSF identified 1,674 (TMT) and 441 (LFQ) proteins. Protein profiles associated with clinical improvement reflected the reconstitution of neuronal circuits. Additionally, clinical improvement was associated with reduced humoral mediators of the immune response such as complement factors and immunoglobulins and cellular mediators such as lymphocytes. Discussion: Our multi-proteomic analysis provides new insights into the pathobiology of SMA and defines potential biomarker profiles in CSF for the disease course under nusinersen therapy.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_02:25:42.401.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Uwe Warnken
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-14 14:19:17	ID requested
⏵ 1	2025-05-07 02:25:43	announced

10.1007/s00415-025-12984-7;

Cebulla G, Hai L, Warnken U, G, ü, ng, ö, r C, Hoffmann DC, Korporal-Kuhnke M, Wildemann B, Wick W, Kessler T, Weiler M, Long-term CSF responses in adult patients with spinal muscular atrophy type 2 or 3 on treatment with nusinersen. J Neurol, 272(4):270(2025) [pubmed]

submitter keyword: cerebrospinal fluid, TMT, nusinersen,spinal muscle atrophy, SMA, CSF

Prof. Dr. med. Wolfgang Wick
contact affiliation	Clinical Cooperation Unit Neurooncology B320 German Cancer Research Center Heidelberg
contact email	w.wick@dkfz-heidelberg.de
lab head
Uwe Warnken
contact affiliation	German Cancer Research Center Heidelberg, Clinical Cooperation Unit Neurooncology B320
contact email	u.warnken@dkfz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054900
     1. Label: PRIDE project
     2. Name: Longitudinal Proteomic Fingerprinting in CSF of Nusinersen-Treated Patients with 5q-Associated Spinal Muscular Atrophy