PXD060060

PXD060060 is an original dataset announced via ProteomeXchange.

Title	Multiomics profiling in Spinal Muscular Atrophy (SMA): Insights from longitudinal CSF analysis of patients under treatment with Nusinersen
Description	Spinal Muscular Atrophy (SMA) is a rare neuromuscular disease caused by biallelic mutations in the SMN1 gene, leading to progressive muscle weakness due to degeneration of the anterior horn cells. Since 2017, SMA patients can be treated with the anti-sense oligonucleotide Nusinersen, which promotes alternative splicing of the SMN2 gene, by regular intrathecal injections. In this prospective study we applied metabol-, lipid-, and proteomic analysis to examine sequential CSF samples from 13 SMA patients and controls. This multiomic approach identified over 800 proteins and 400 small molecules including lipids. Multivariate analysis of multiomic data successfully discriminated between the CSF derived from SMA patients and control subjects. Lipidomic analysis revealed increased levels of cholesteryl esters and lyso-phospholipids, along with reduced levels of cholesterol and phospholipids in the CSF of SMA patients as compared to the healthy control group. This data, combined with results from functional assays, led us to conclude that SMA patients exhibit altered levels and function of HDL-like particles in the CSF. Notably, Nusinersen therapy was observed to reverse disease-specific profile changes towards a physiological state, potentially explicable by restoring HDL-function.
HostingRepository	PRIDE
AnnounceDate	2025-04-01
AnnouncementXML	Submission_2025-04-01_13:11:33.380.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Darnhofer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-22 03:54:13	ID requested
⏵ 1	2025-04-01 13:11:33	announced

10.1007/S00415-025-12909-4;

submitter keyword: proteomics, Nusinersen,SMA, Multi-omics

Harald Koefeler
contact affiliation	Priv. Doz. Dr. Harald C. Köfeler Director Core Facility Mass Spectrometry Medical University Graz Center for Medical Research (ZMF) Neue Stiftingtalstrasse 6 8010 Graz AUSTRIA
contact email	harald.koefeler@medunigraz.at
lab head
Barbara Darnhofer
contact affiliation	Omics Center Graz
contact email	barbara.darnhofer@klinikum-graz.at
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/04/PXD060060

PRIDE project URI

• PRIDE
  1. PXD060060
     1. Label: PRIDE project
     2. Name: Multiomics profiling in Spinal Muscular Atrophy (SMA): Insights from longitudinal CSF analysis of patients under treatment with Nusinersen