New orphan disease therapies from the proteome of industrial plasma processing waste- a treatment for aceruloplasminemia
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Published:2024-01-30
Issue:1
Volume:7
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Zanardi Alan, Nardini Ilaria, Raia Sara, Conti Antonio, Ferrini Barbara, D’Adamo PatriziaORCID, Gilberti Enrica, DePalma GiuseppeORCID, Belloli SaraORCID, Monterisi Cristina, Coliva AngelaORCID, Rainone PaoloORCID, Moresco Rosa Maria, Mori Filippo, Zurlo Giada, Scali Carla, Natali Letizia, Pancanti Annalisa, Giovacchini Pierangelo, Magherini GiulioORCID, Tovani Greta, Salvini Laura, Cicaloni Vittoria, Tinti Cristina, Tinti Laura, Lana DanieleORCID, Magni GiadaORCID, Giovannini Maria GraziaORCID, Gringeri Alessandro, Caricasole AndreaORCID, Alessio MassimoORCID
Abstract
AbstractPlasma-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.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
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