{
  "abstract": "Mucopolysaccharidosis Type II (MPS-II) is a rare X-linked lysosomal storage disorder, characterized by deficiency of the lysosomal hydrolase iduronate 2-sulphatase (IDS). Cardiac impairments contribute to mortality in patients. Enzyme replacement therapy (ERT) with Idursulfase is a promising treatment for the cardiac dysfunction. We compared the proteome changes following intravenous (IV) with and without adjunct nebulized ERT in IDS-KO mice. Male mice were assigned to 4 groups: 1) WT IV + nebulized saline (WT; n=8); 2) IDS-KO IV + nebulized saline (KO; n=5); 3) IDS-KO IV Idursulfase (1 mg/kg; KO-IV, n=5); 4) IDS-KO IV (1 mg/kg) + nebulized Idursulfase (0.33 mg/mouse; KO-NEB, n=5). Treatments were administered once a week starting at 8 weeks of age and the heart was harvested 12 weeks post-ERT. Mouse heart samples were prepared for global proteomics measurements with Nano-liquid chromatography tandem mass spectrometry (n=3/group; Nano-LC/MS/MS). Global limma moderated F-test analysis identified 928 differently abundant proteins across the four groups. Pairwise Euclidean distances from the IDS-KO were significantly greater for the KO-NEB vs KO-IV group (47.5, 3.7 vs 40.8, 1.1; p < 0.001), showing that adjunct nebulization elicited a more profound proteomic shift than IV alone. The mean z-score compartment analysis revealed that the subcellular compartment protein profile of KO-NEB shifted towards the WT profile, whereas this pattern was less evident in KO-IV. The cluster analysis also revealed treatment-specific and rescue-like protein modules. Overall, our results suggest that adjunctive nebulized Idursulfase ERT enhances the cardiac proteomic changes caused by IV treatment in IDS-KO mice. Proteomics data are available via ProteomeXchange with identifier PXD083242.",
  "abstract_shown": true,
  "affiliations": [
    "Duke University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "V. M. Mariani"
    },
    {
      "name": "A. Labilloy"
    },
    {
      "name": "W. T. Cade"
    },
    {
      "affs": [
        0
      ],
      "name": "P. R. Ferreira"
    },
    {
      "affs": [
        0
      ],
      "name": "L. F. Ferreira"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a46kptf7wewn2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.07.749889",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749889v1.full",
  "id": "a46kptf7wewn2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749889v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2737|Lysosomal Storage Disorders Research"
    ]
  ],
  "openalex": "W7212317217",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749889v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a46kptf7wewn2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:09Z",
      "native_id": "10.64898/2026.09.07.749889",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749889v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Adjunctive nebulization of Idursulfase to intravenous treatment enhances cardiac proteome adaptations in IDS-KO mice",
  "title_text": "Adjunctive nebulization of Idursulfase to intravenous treatment enhances cardiac proteome adaptations in IDS-KO mice",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:09Z",
  "url": "https://research.draconitic.com/paper/a46kptf7wewn2",
  "venue": "bioRxiv",
  "versions": []
}