PXD015117-1

PXD015117 is an original dataset announced via ProteomeXchange.

Title	Cerebrospinal fluid proteomic profiling in nusinersen-treated patients with spinal muscular atrophy
Description	Background: Promising results from recent clinical trials on the approved antisense oligonucleotide nusinersen in pediatric patients with 5q-linked spinal muscular atrophy (SMA) still have to be confirmed in adult patients but are hindered by a lack of sensitive biomarkers that indicate an early therapeutic response. Changes of the overall neurochemical composition of cerebrospinal fluid (CSF) under therapy may yield additive diagnostic and predictive information. Methods: In this prospective proof-of-concept and feasibility study, we evaluated non-targeted CSF proteomic profiles by mass spectrometry along with basic CSF parameters of ten adult patients with SMA types II or III before and after ten months of nusinersen therapy, in comparison with ten age- and gender-matched controls. These data were bioinformatically analyzed and correlated with clinical outcomes assessed by the Hammersmith Functional Rating Scale Expanded (HFMSE). Results: CSF proteomic profiles of patients with SMA differed from controls. Two groups of SMA patients were identified based on unsupervised clustering. These groups differed in age and expression of proteins related to neuroregeneration or neurodegeneration. Intraindividual CSF differences in response to nusinersen treatment varied between patients who clinically improved and those who did not. Conclusions: Comparative CSF proteomic analysis in adult SMA patients before and after treatment identified subgroups and treatment-related changes and may therefore be suitable for diagnostic and predictive analysis. These results require verification in larger multicenter cohorts.
HostingRepository	PRIDE
AnnounceDate	2019-12-18
AnnouncementXML	Submission_2019-12-18_10:09:50.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tobias Kessler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-21 08:51:36	ID requested
⏵ 1	2019-12-18 10:09:51	announced

Dataset with its publication pending

submitter keyword: SMA, proteomic profiling

Wolfgang Wick
contact affiliation	Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
contact email	wolfgang.wick@med.uni-heidelberg.de
lab head
Tobias Kessler
contact affiliation	Clinical Cooperation Unit Neurooncology, German Cancer Research Center
contact email	t.kessler@dkfz.de
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/2019/12/PXD015117

PRIDE project URI

• PRIDE
  1. PXD015117
     1. Label: PRIDE project
     2. Name: Cerebrospinal fluid proteomic profiling in nusinersen-treated patients with spinal muscular atrophy