{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:15:10Z","timestamp":1793153710941,"version":"4.5.0"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016471","name":"Agios Pharmaceuticals, Inc.","doi-asserted-by":"crossref","award":["research collaborative grant"],"award-info":[{"award-number":["research collaborative grant"]}],"id":[{"id":"10.13039\/100016471","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003407","name":"MIUR","doi-asserted-by":"crossref","award":["PRIN (2020) #2020Z22PM7"],"award-info":[{"award-number":["PRIN (2020) #2020Z22PM7"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,23]]},"abstract":"<jats:p>\n                    Hereditary spherocytosis (HS) is the most common, nonimmune, hereditary, chronic hemolytic anemia after hemoglobinopathies. The genetic defects in membrane function causing HS lead to perturbation of the RBC metabolome, with altered glycolysis. In mice genetically lacking protein 4.2 (4.2\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ; Epb42), a murine model of HS, we showed increased expression of pyruvate kinase (PK) isoforms in whole and fractioned RBCs in conjunction with abnormalities in the glycolytic pathway and in the glutathione (GSH) system. Mitapivat, a PK activator, metabolically reprogrammed 4.2\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mouse RBCs with amelioration of glycolysis and the GSH cycle. This resulted in improved osmotic fragility, reduced phosphatidylserine positivity, amelioration of RBC cation content, reduction of Na\/K\/Cl cotransport and Na\/H-exchange overactivation, and decrease in erythroid vesicles release in vitro. Mitapivat treatment significantly decreased erythrophagocytosis and beneficially affected iron homeostasis. In mild-to-moderate HS, the beneficial effect of splenectomy is still controversial. Here, we showed that splenectomy improves anemia in 4.2\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice and that mitapivat is noninferior to splenectomy. An additional benefit of mitapivat treatment was lower expression of markers of inflammatory vasculopathy in 4.2\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice with or without splenectomy, indicating a multisystemic action of mitapivat. These findings support the notion that mitapivat treatment should be considered for symptomatic HS.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.172656","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T12:01:17Z","timestamp":1694088077000},"source":"Crossref","is-referenced-by-count":17,"title":["Mitapivat reprograms the RBC metabolome and improves anemia in a mouse model of hereditary spherocytosis"],"prefix":"10.1172","volume":"8","author":[{"given":"Alessandro","family":"Matte","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Verona, and Azienda Ospedaliera Universitaria Verona, Policlinico GB Rossi, Verona, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand B.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Verona, and Azienda Ospedaliera Universitaria Verona, Policlinico GB Rossi, Verona, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6208-8130","authenticated-orcid":true,"given":"Federica","family":"Gevi","sequence":"additional","affiliation":[{"name":"Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Federti","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Verona, and Azienda Ospedaliera Universitaria Verona, Policlinico GB Rossi, Verona, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Recchiuti","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral, and Biotechnology Science, \u201cG.d\u2019Annunzio\u201d University of Chieti \u2013 Pescara, Center for Advanced Studies and Technology, Chieti, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1669-3775","authenticated-orcid":true,"given":"Giulia","family":"Ferri","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral, and Biotechnology Science, \u201cG.d\u2019Annunzio\u201d University of Chieti \u2013 Pescara, Center for Advanced Studies and Technology, Chieti, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Brunati","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padua, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Angelo","family":"Pagano","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padua, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3624-7721","authenticated-orcid":true,"given":"Roberta","family":"Russo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, Naples, Italy."},{"name":"CEINGE Biotecnologie Avanzate, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6537-0550","authenticated-orcid":true,"given":"Christophe","family":"Leboeuf","sequence":"additional","affiliation":[{"name":"INSERM, Paris, France."},{"name":"Universit\u00e9 Paris 7 \u2014 Denis Diderot, Paris, France."},{"name":"Assistance Publique \u2014 H\u00f4pitaux de Paris, H\u00f4pital Saint-Louis, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Janin","sequence":"additional","affiliation":[{"name":"INSERM, Paris, France."},{"name":"Universit\u00e9 Paris 7 \u2014 Denis Diderot, Paris, France."},{"name":"Assistance Publique \u2014 H\u00f4pitaux de Paris, H\u00f4pital Saint-Louis, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8457-042X","authenticated-orcid":true,"given":"Anna Maria","family":"Timperio","sequence":"additional","affiliation":[{"name":"Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille","family":"Iolascon","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, Naples, Italy."},{"name":"CEINGE Biotecnologie Avanzate, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-4212","authenticated-orcid":true,"given":"Elisa","family":"Gremese","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology, Fondazione Policlinico Universitario A. 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