New orphan disease therapies from the proteome of industrial plasma processing waste- a treatment for aceruloplasminemia.

Journal

Communications biology

ISSN: 2399-3642

Titre abrégé: Commun Biol

Pays: England

ID NLM: 101719179

Informations de publication

Date de publication:
30 Jan 2024

Historique:

received: 17 08 2023

accepted: 15 01 2024

medline: 31 1 2024

pubmed: 31 1 2024

entrez: 30 1 2024

Statut: epublish

Résumé

Plasma-derived therapeutic proteins are produced through an industrial fractionation process where proteins are purified from individual intermediates, some of which remain unused and are discarded. Relatively few plasma-derived proteins are exploited clinically, with most of available plasma being directed towards the manufacture of immunoglobulin and albumin. Although the plasma proteome provides opportunities to develop novel protein replacement therapies, particularly for rare diseases, the high cost of plasma together with small patient populations impact negatively on the development of plasma-derived orphan drugs. Enabling therapeutics development from unused plasma fractionation intermediates would therefore constitute a substantial innovation. To this objective, we characterized the proteome of unused plasma fractionation intermediates and prioritized proteins for their potential as new candidate therapies for human disease. We selected ceruloplasmin, a plasma ferroxidase, as a potential therapy for aceruloplasminemia, an adult-onset ultra-rare neurological disease caused by iron accumulation as a result of ceruloplasmin mutations. Intraperitoneally administered ceruloplasmin, purified from an unused plasma fractionation intermediate, was able to prevent neurological, hepatic and hematological phenotypes in ceruloplasmin-deficient mice. These data demonstrate the feasibility of transforming industrial waste plasma fraction into a raw material for manufacturing of new candidate proteins for replacement therapies, optimizing plasma use and reducing waste generation.

Identifiants

DOI: 10.1038/s42003-024-05820-7 PMID: 38291108

pubmed: 38291108

doi: 10.1038/s42003-024-05820-7

pii: 10.1038/s42003-024-05820-7

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

140

Informations de copyright

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