In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related Injury
Drug repurposing is a valuable strategy for rare diseases. Sickle cell disease (SCD) is a rare hereditary hemolytic anemia accompanied by acute and chronic painful episodes, most often in the context of vaso-occlusive crisis (VOC). Although progress in the knowledge of pathophysiology of SCD have al...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-03-01
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| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000848 |
| _version_ | 1797225582407188480 |
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| author | Enrica Federti Alessandro Matte Antonio Recchiuti Francesca Garello Alessandra Ghigo Wassim El Nemer Enzo Terreno Angela Amoresano Domenico Mattoscio Franco Turrini Christophe Lebouef Anne Janin Antonella Pantaleo Roberta Russo Mickael Marin Iana Iatcencko Veronica Riccardi Angela Siciliano Achille Iolascon Carlo Brugnara Lucia De Franceschi |
| author_facet | Enrica Federti Alessandro Matte Antonio Recchiuti Francesca Garello Alessandra Ghigo Wassim El Nemer Enzo Terreno Angela Amoresano Domenico Mattoscio Franco Turrini Christophe Lebouef Anne Janin Antonella Pantaleo Roberta Russo Mickael Marin Iana Iatcencko Veronica Riccardi Angela Siciliano Achille Iolascon Carlo Brugnara Lucia De Franceschi |
| author_sort | Enrica Federti |
| collection | DOAJ |
| description | Drug repurposing is a valuable strategy for rare diseases. Sickle cell disease (SCD) is a rare hereditary hemolytic anemia accompanied by acute and chronic painful episodes, most often in the context of vaso-occlusive crisis (VOC). Although progress in the knowledge of pathophysiology of SCD have allowed the development of new therapeutic options, a large fraction of patients still exhibits unmet therapeutic needs, with persistence of VOCs and chronic disease progression. Here, we show that imatinib, an oral tyrosine kinase inhibitor developed for the treatment of chronic myelogenous leukemia, acts as multimodal therapy targeting signal transduction pathways involved in the pathogenesis of both anemia and inflammatory vasculopathy of humanized murine model for SCD. In addition, imatinib inhibits the platelet-derived growth factor-B–dependent pathway, interfering with the profibrotic response to hypoxia/reperfusion injury, used to mimic acute VOCs. Our data indicate that imatinib might be considered as possible new therapeutic tool for chronic treatment of SCD. |
| first_indexed | 2024-04-24T14:11:18Z |
| format | Article |
| id | doaj.art-c8c05eebb53a44d484b867d2b88dc0d7 |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-04-24T14:11:18Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-c8c05eebb53a44d484b867d2b88dc0d72024-04-03T09:24:06ZengWileyHemaSphere2572-92412023-03-0173e84810.1097/HS9.0000000000000848202303000-00017In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related InjuryEnrica Federti0Alessandro Matte1Antonio Recchiuti2Francesca Garello3Alessandra Ghigo4Wassim El Nemer5Enzo Terreno6Angela Amoresano7Domenico Mattoscio8Franco Turrini9Christophe Lebouef10Anne Janin11Antonella Pantaleo12Roberta Russo13Mickael Marin14Iana Iatcencko15Veronica Riccardi16Angela Siciliano17Achille Iolascon18Carlo Brugnara19Lucia De Franceschi201 Department of Medicine, University of Verona & AOUI Verona, Policlinico GB Rossi, Verona, Italy1 Department of Medicine, University of Verona & AOUI Verona, Policlinico GB Rossi, Verona, Italy2 Department of Medical, Oral, and Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” Chieti-Pescara, Italy3 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy3 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy4 Etablissement Français du Sang, UMR 7268 ADES, Faculte de Medicine Timone, Marseille, France3 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy5 Department of Chemical Sciences, University Federico II of Napoli, Italy2 Department of Medical, Oral, and Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” Chieti-Pescara, Italy6 Department of Oncology, University of Torino, Italy7 INSERM, U1165, Paris, France7 INSERM, U1165, Paris, France10 University of Sassari, Italy11 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, and CEINGE Biotecnologie Avanzate, Naples, Italy4 Etablissement Français du Sang, UMR 7268 ADES, Faculte de Medicine Timone, Marseille, France1 Department of Medicine, University of Verona & AOUI Verona, Policlinico GB Rossi, Verona, Italy1 Department of Medicine, University of Verona & AOUI Verona, Policlinico GB Rossi, Verona, Italy1 Department of Medicine, University of Verona & AOUI Verona, Policlinico GB Rossi, Verona, Italy11 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, and CEINGE Biotecnologie Avanzate, Naples, Italy12 Department of Laboratory Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA1 Department of Medicine, University of Verona & AOUI Verona, Policlinico GB Rossi, Verona, ItalyDrug repurposing is a valuable strategy for rare diseases. Sickle cell disease (SCD) is a rare hereditary hemolytic anemia accompanied by acute and chronic painful episodes, most often in the context of vaso-occlusive crisis (VOC). Although progress in the knowledge of pathophysiology of SCD have allowed the development of new therapeutic options, a large fraction of patients still exhibits unmet therapeutic needs, with persistence of VOCs and chronic disease progression. Here, we show that imatinib, an oral tyrosine kinase inhibitor developed for the treatment of chronic myelogenous leukemia, acts as multimodal therapy targeting signal transduction pathways involved in the pathogenesis of both anemia and inflammatory vasculopathy of humanized murine model for SCD. In addition, imatinib inhibits the platelet-derived growth factor-B–dependent pathway, interfering with the profibrotic response to hypoxia/reperfusion injury, used to mimic acute VOCs. Our data indicate that imatinib might be considered as possible new therapeutic tool for chronic treatment of SCD.http://journals.lww.com/10.1097/HS9.0000000000000848 |
| spellingShingle | Enrica Federti Alessandro Matte Antonio Recchiuti Francesca Garello Alessandra Ghigo Wassim El Nemer Enzo Terreno Angela Amoresano Domenico Mattoscio Franco Turrini Christophe Lebouef Anne Janin Antonella Pantaleo Roberta Russo Mickael Marin Iana Iatcencko Veronica Riccardi Angela Siciliano Achille Iolascon Carlo Brugnara Lucia De Franceschi In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related Injury HemaSphere |
| title | In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related Injury |
| title_full | In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related Injury |
| title_fullStr | In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related Injury |
| title_full_unstemmed | In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related Injury |
| title_short | In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related Injury |
| title_sort | in humanized sickle cell mice imatinib protects against sickle cell related injury |
| url | http://journals.lww.com/10.1097/HS9.0000000000000848 |
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