Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784766440292745216
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
work_keys_str_mv AT romanonicola longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT baiardigiammarco longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT pintovaleriamaria longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT quintinosabrina longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT gianesinbarbara longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT sassoriccardo longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT diociasiandrea longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT mattiolifrancesca longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT marcheseroberta longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT abbruzzesegiovanni longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT castaldiantonio longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy
AT fornigianluca longtermneuroradiologicalandclinicalevaluationofnbiapatientstreatedwithadeferipronebasedironchelationtherapy