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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369383/ https://www.ncbi.nlm.nih.gov/pubmed/35956138 http://dx.doi.org/10.3390/jcm11154524 |
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author | Romano, Nicola Baiardi, Giammarco Pinto, Valeria Maria Quintino, Sabrina Gianesin, Barbara Sasso, Riccardo Diociasi, Andrea Mattioli, Francesca Marchese, Roberta Abbruzzese, Giovanni Castaldi, Antonio Forni, Gian Luca |
author_facet | Romano, Nicola Baiardi, Giammarco Pinto, Valeria Maria Quintino, Sabrina Gianesin, Barbara Sasso, Riccardo Diociasi, Andrea Mattioli, Francesca Marchese, Roberta Abbruzzese, Giovanni Castaldi, Antonio Forni, Gian Luca |
author_sort | Romano, Nicola |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9369383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93693832022-08-12 Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy Romano, Nicola Baiardi, Giammarco Pinto, Valeria Maria Quintino, Sabrina Gianesin, Barbara Sasso, Riccardo Diociasi, Andrea Mattioli, Francesca Marchese, Roberta Abbruzzese, Giovanni Castaldi, Antonio Forni, Gian Luca J Clin Med Article 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. MDPI 2022-08-03 /pmc/articles/PMC9369383/ /pubmed/35956138 http://dx.doi.org/10.3390/jcm11154524 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Romano, Nicola Baiardi, Giammarco Pinto, Valeria Maria Quintino, Sabrina Gianesin, Barbara Sasso, Riccardo Diociasi, Andrea Mattioli, Francesca Marchese, Roberta Abbruzzese, Giovanni Castaldi, Antonio Forni, Gian Luca Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369383/ https://www.ncbi.nlm.nih.gov/pubmed/35956138 http://dx.doi.org/10.3390/jcm11154524 |
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