Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy
Neurodegeneration with brain iron accumulation (NBIA) comprises various rare clinical entities with brain iron overload as a common feature. Magnetic resonance imaging (MRI) allows diagnosis of this condition, and genetic molecular testing can confirm the diagnosis to better understand the intracell...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/15/4524 |
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| author | Nicola Romano Giammarco Baiardi Valeria Maria Pinto Sabrina Quintino Barbara Gianesin Riccardo Sasso Andrea Diociasi Francesca Mattioli Roberta Marchese Giovanni Abbruzzese Antonio Castaldi Gian Luca Forni |
| author_facet | Nicola Romano Giammarco Baiardi Valeria Maria Pinto Sabrina Quintino Barbara Gianesin Riccardo Sasso Andrea Diociasi Francesca Mattioli Roberta Marchese Giovanni Abbruzzese Antonio Castaldi Gian Luca Forni |
| author_sort | Nicola Romano |
| collection | DOAJ |
| description | Neurodegeneration with brain iron accumulation (NBIA) comprises various rare clinical entities with brain iron overload as a common feature. Magnetic resonance imaging (MRI) allows diagnosis of this condition, and genetic molecular testing can confirm the diagnosis to better understand the intracellular damage mechanism involved. NBIA groups disorders include: pantothenate kinase-associated neurodegeneration (PKAN), mutations in the gene encoding pantothenate kinase 2 (PANK2); neuroferritinopathy, mutations in the calcium-independent phospholipase A2 gene (PLA2G6); aceruloplasminemia; and other subtypes with no specific clinical or MRI specific patterns identified. There is no causal therapy, and only symptom treatments are available for this condition. Promising strategies include the use of deferiprone (DFP), an orally administered bidentate iron chelator with the ability to pass through the blood–brain barrier. This is a prospective study analysis with a mean follow-up time of 5.5 ± 2.3 years (min–max: 2.4–9.6 years) to define DFP (15 mg/kg bid)’s efficacy and safety in the continuous treatment of 10 NBIA patients through clinical and neuroradiological evaluation. Our results show the progressive decrease in the cerebral accumulation of iron evaluated by MRI and a substantial stability of the overall clinical neurological picture without a significant correlation between clinical and radiological findings. Complete ferrochelation throughout the day appears to be of fundamental importance considering that oxidative damage is generated, above, all by non-transferrin-bound iron (NTBI); thus, we hypothesize that a (TID) administration regimen of DFP might better apply its chelating properties over 24 h with the aim to also obtain clinical improvement beyond the neuroradiological improvement. |
| first_indexed | 2024-03-09T10:07:58Z |
| format | Article |
| id | doaj.art-eef2e73b533f42fc957f730697a72ee0 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T10:07:58Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-eef2e73b533f42fc957f730697a72ee02023-12-01T22:59:56ZengMDPI AGJournal of Clinical Medicine2077-03832022-08-011115452410.3390/jcm11154524Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation TherapyNicola Romano0Giammarco Baiardi1Valeria Maria Pinto2Sabrina Quintino3Barbara Gianesin4Riccardo Sasso5Andrea Diociasi6Francesca Mattioli7Roberta Marchese8Giovanni Abbruzzese9Antonio Castaldi10Gian Luca Forni11Department of Diagnostic and Interventional Neuroradiology, EO Ospedali Galliera, 16128 Genoa, ItalyClinical Pharmacology Unit, EO Ospedali Galliera, 16128 Genoa, ItalyCentro della Microcitemia, delle Anemie Congenite e dei Disordini del Metabolismo del Ferro, EO Ospedali Galliera, 16128 Genoa, ItalyCentro della Microcitemia, delle Anemie Congenite e dei Disordini del Metabolismo del Ferro, EO Ospedali Galliera, 16128 Genoa, ItalyCentro della Microcitemia, delle Anemie Congenite e dei Disordini del Metabolismo del Ferro, EO Ospedali Galliera, 16128 Genoa, ItalyDepartment of Diagnostic and Interventional Neuroradiology, EO Ospedali Galliera, 16128 Genoa, ItalyDepartment of Health Sciences (DISSAL), Radiology Section, University of Genoa, 16132 Genoa, ItalyClinical Pharmacology Unit, EO Ospedali Galliera, 16128 Genoa, ItalyIRCCS Policlinico San Martino, 16132 Genoa, ItalyClinical Neurophysiology, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, 16132 Genoa, ItalyDepartment of Diagnostic and Interventional Neuroradiology, EO Ospedali Galliera, 16128 Genoa, ItalyCentro della Microcitemia, delle Anemie Congenite e dei Disordini del Metabolismo del Ferro, EO Ospedali Galliera, 16128 Genoa, ItalyNeurodegeneration with brain iron accumulation (NBIA) comprises various rare clinical entities with brain iron overload as a common feature. Magnetic resonance imaging (MRI) allows diagnosis of this condition, and genetic molecular testing can confirm the diagnosis to better understand the intracellular damage mechanism involved. NBIA groups disorders include: pantothenate kinase-associated neurodegeneration (PKAN), mutations in the gene encoding pantothenate kinase 2 (PANK2); neuroferritinopathy, mutations in the calcium-independent phospholipase A2 gene (PLA2G6); aceruloplasminemia; and other subtypes with no specific clinical or MRI specific patterns identified. There is no causal therapy, and only symptom treatments are available for this condition. Promising strategies include the use of deferiprone (DFP), an orally administered bidentate iron chelator with the ability to pass through the blood–brain barrier. This is a prospective study analysis with a mean follow-up time of 5.5 ± 2.3 years (min–max: 2.4–9.6 years) to define DFP (15 mg/kg bid)’s efficacy and safety in the continuous treatment of 10 NBIA patients through clinical and neuroradiological evaluation. Our results show the progressive decrease in the cerebral accumulation of iron evaluated by MRI and a substantial stability of the overall clinical neurological picture without a significant correlation between clinical and radiological findings. Complete ferrochelation throughout the day appears to be of fundamental importance considering that oxidative damage is generated, above, all by non-transferrin-bound iron (NTBI); thus, we hypothesize that a (TID) administration regimen of DFP might better apply its chelating properties over 24 h with the aim to also obtain clinical improvement beyond the neuroradiological improvement.https://www.mdpi.com/2077-0383/11/15/4524NBIAdeferipronebrain ironiron overloadneurodegeneration |
| spellingShingle | Nicola Romano Giammarco Baiardi Valeria Maria Pinto Sabrina Quintino Barbara Gianesin Riccardo Sasso Andrea Diociasi Francesca Mattioli Roberta Marchese Giovanni Abbruzzese Antonio Castaldi Gian Luca Forni Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy Journal of Clinical Medicine NBIA deferiprone brain iron iron overload neurodegeneration |
| title | Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy |
| title_full | Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy |
| title_fullStr | Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy |
| title_full_unstemmed | Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy |
| title_short | Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy |
| title_sort | long term neuroradiological and clinical evaluation of nbia patients treated with a deferiprone based iron chelation therapy |
| topic | NBIA deferiprone brain iron iron overload neurodegeneration |
| url | https://www.mdpi.com/2077-0383/11/15/4524 |
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