PXD054411-1

PXD054411 is an original dataset announced via ProteomeXchange.

Title	Nebulized and intravenous enzyme replacement therapy in mice with mucopolysaccharidosis type II
Description	Mucopolysaccharidosis Type II is a hereditary lysosomal storage disease characterized by deficiency in the enzyme iduronate 2-sulfatase (IDS). IDS is critical in the breakdown of sulfated glycosaminoglycans and its deficiency leads to an accumulation of these compounds across various tissue types resulting in multisystemic dysfunction. Intravenous administration of recombinant IDS (idursulfase) substantially improves patients’ quality and length of life. However, recombinant IDS delivered intravenously is sequestered in the liver and respiratory failure remains as the leading cause of death for patients independent of idursulfase treatment, which suggests insufficient delivery to the lungs. This study aimed to assess a novel method of idursulfase administration by nebulizer in combination with intravenous treatment and determine if this route of administration may improve lung delivery of idursulfase and overall pathology. To fulfill this aim, whole body IDS knockout mice underwent twelve weeks of intravenous or combination treatment. Liver and lung tissue were harvested seven days after the last treatment. IDS activity, histological markers, and global proteomics from treated groups were compared to untreated knockouts or wild-type mice. Increased enzyme activity and histological measurements indicated augmented delivery to the liver with the combined treatment, but lung enzyme activity with each treatment was similar to untreated animals. However, proteomics data demonstrated that both treatments attenuated key features of the disease, although it is unclear whether the addition of nebulized administration improved efficacy in the lungs.
HostingRepository	PRIDE
AnnounceDate	2025-06-09
AnnouncementXML	Submission_2025-06-09_14:11:55.750.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Leonardo Ferreira
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-30 15:13:25	ID requested
⏵ 1	2025-06-09 14:11:56	announced

10.1101/2024.09.03.611097;

submitter keyword: enzyme replacement therapy,MPSII

Leonardo Ferreira
contact affiliation	Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, North Carolina, United States of America
contact email	leonardo.ferreira@duke.edu
lab head
Leonardo Ferreira
contact affiliation	Duke University
contact email	leonardo.ferreira@duke.edu
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/2025/06/PXD054411

PRIDE project URI

• PRIDE
  1. PXD054411
     1. Label: PRIDE project
     2. Name: Nebulized and intravenous enzyme replacement therapy in mice with mucopolysaccharidosis type II