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

Autor: Zanardi A; Proteome Biochemistry, COSR-Centre for Omics Sciences, IRCCS Ospedale San Raffaele, Milano, Italy., Nardini I; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Raia S; Proteome Biochemistry, COSR-Centre for Omics Sciences, IRCCS Ospedale San Raffaele, Milano, Italy., Conti A; Proteome Biochemistry, COSR-Centre for Omics Sciences, IRCCS Ospedale San Raffaele, Milano, Italy., Ferrini B; Proteome Biochemistry, COSR-Centre for Omics Sciences, IRCCS Ospedale San Raffaele, Milano, Italy., D'Adamo P; Mouse Behavior Facility, IRCCS Ospedale San Raffaele, Milano, Italy., Gilberti E; Unit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy., DePalma G; Unit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy., Belloli S; Nuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San Raffaele, Milano, Italy.; Institute of Molecular Bioimaging and Physiology-IBFM, CNR, Segrate, Italy., Monterisi C; Nuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San Raffaele, Milano, Italy., Coliva A; Nuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San Raffaele, Milano, Italy., Rainone P; Nuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San Raffaele, Milano, Italy.; Institute of Molecular Bioimaging and Physiology-IBFM, CNR, Segrate, Italy.; Medicine and Surgery Department, University of Milano - Bicocca, Monza, Italy., Moresco RM; Nuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San Raffaele, Milano, Italy.; Institute of Molecular Bioimaging and Physiology-IBFM, CNR, Segrate, Italy.; Medicine and Surgery Department, University of Milano - Bicocca, Monza, Italy., Mori F; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Zurlo G; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Scali C; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Natali L; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Pancanti A; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Giovacchini P; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Magherini G; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Tovani G; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Salvini L; Toscana Life Sciences Foundation, Siena, Italy., Cicaloni V; Toscana Life Sciences Foundation, Siena, Italy., Tinti C; Toscana Life Sciences Foundation, Siena, Italy., Tinti L; Toscana Life Sciences Foundation, Siena, Italy., Lana D; Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Firenze, Italy., Magni G; Institute of Applied Physics 'Nello Carrara', National Research Council (IFAC-CNR), Sesto Fiorentino, Italy., Giovannini MG; Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Firenze, Italy., Gringeri A; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy., Caricasole A; Research and Innovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, Italy. a.caricasole@kedrion.com., Alessio M; Proteome Biochemistry, COSR-Centre for Omics Sciences, IRCCS Ospedale San Raffaele, Milano, Italy. alessio.massimo@hsr.it.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Jan 30; Vol. 7 (1), pp. 140. Date of Electronic Publication: 2024 Jan 30.
DOI: 10.1038/s42003-024-05820-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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