Articolo in rivista, 2024, ENG, 10.1038/s42003-024-05820-7

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

Zanardi A.; Nardini I.; Raia S.; Conti A.; Ferrini B.; D'Adamo P.; Gilberti E.; De Palma G.; Belloli S.; Monterisi C.; Coliva A.; Rainone P.; Moresco R.M.; Mori F.; Zurlo G.; Scali C.; Natali L.; Pancanti A.; Giovacchini P.; Magherini G.; Tovani G.; Salvini L.; Cicaloni V.; Tinti C.; Tinti L.; Lana D.; Magni G.; Giovannini M.G.; Gringeri A.; Caricasole A.; Alessio M.

Proteome Biochemistry, COSR-Centre lor Omics Sciences, IRCCS Ospedale San Raffaele, Milano, ltaly. Research and lnnovation, Kedrion S.p.A., Loc, Bolognana, Gallicano, ltaly. Mouse Behavior Facility, IRCCS Ospedale San Raffaele, Milano, ltaly. Unit of Occupational Health and Industriai Hygiene, Department of Medicai and Surgical Specialties, Radiologica! Sciences and Public Health, University of Brescia, Brescia, ltaly. Nuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San Raffaele, Milano, ltaly. lnstitute of Molecular Bioimaging and Physiology-lBFM, CNR, Segrate, ltaly. Medicine and Surgery Department, University of Milano - Bicocca, Monza, ltaly. Toscana Life Sciences Foundation, Siena, ltaly. Department of Health Sciences, Section of Clinica! Pharmacology and Oncology, University of Florence, Firenze, ltaly. lnstitute of Applied Physics "Nello Carrara", National Research Council (IFAC­CNR), Sesto Fiorentino, ltaly

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.

Communications biology 7 (1), pp. 140–?

Keywords

aceruloplasminemia

CNR authors

Moresco Rosa Maria, Magni Giada, Belloli Sara, Rainone Paolo

CNR institutes

IBFM – Istituto di bioimmagini e fisiologia molecolare