Targeting pro-oxidant iron with deferoxamine as a treatment for ischemic stroke: safety and optimal dose selection in a randomized clinical trial

A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form o...

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Detalles Bibliográficos
Autores: Millán Torné, Mònica, De Gregorio Rocasolano, Núria, Pérez de la Ossa, Natalia, Reverté, Silvia, Costa Pagès, Joan, Giner Boya, Pilar, Silva Blas, Yolanda, Sobrino, Tomás, Rodríguez Yañez, Manuel, Nombela Merchán, Florentino, Campos Sanchez, Francisco Sergio, Serena Leal, Joaquín, Vivancos Azor, José Miguel, Martí Sistac, Octavi, Cortés Martínez, Jordi|||0000-0002-3764-0795, Dávalos Errando, Antoni, Gasull, Teresa
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/359852
Acceso en línea:https://hdl.handle.net/2117/359852
https://dx.doi.org/10.3390/antiox10081270
Access Level:acceso abierto
Palabra clave:Multivariate analysis
Biomathematics
Iron
Deferoxamine
Antioxidant
Ferroptosis
Neuroprotection
Outcome
Anàlisi multivariable
Biomatemàtica
Classificació AMS::62 Statistics::62H Multivariate analysis
Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística aplicada::Estadística biosanitària
Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències
Descripción
Sumario:A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40–60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40–60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50–58% of the 40–60 mg/Kg/day DFO-treated patients.

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