Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke

The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and ev...

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Detalles Bibliográficos
Autores: Pérez-Mato, María, Dopico-López, Antonio, Akkoc, Yunus, López-Amoedo, Sonia, Correa-Paz, Clara, Candamo-Lourido, María, Iglesias-Rey, Ramón, López-Arias, Esteban, Bugallo-Casal, Ana, da Silva-Candal, Andrés, Bravo, Susana B, Chantada-Vázquez, María Del Pilar, Arias, Susana, Santamaría-Cadavid, María, Estany-Gestal, Ana, Zaghmi, Ahlem, Gauthier, Marc A, Gutiérrez-Fernández, María, Martin, Abraham, Llop Roig, Jordi, Rodríguez González, Cristina, Almeida, Ángeles, Migliavacca, Martina, Polo, Ester, Pelaz, Beatriz, Gozuacik, Devrim, El Yamani, Naouale, SenGupta, Tanima, Rundén-Pran, Elise, Vivancos, José, Castellanos, Mar, Díez-Tejedor, Exuperio, Sobrino, Tomás, Rabinkov, Aharon, Mirelman, David, Castillo, José, Campos, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/372002
Acceso en línea:http://hdl.handle.net/10261/372002
https://api.elsevier.com/content/abstract/scopus_id/85207374766
Access Level:acceso abierto
Palabra clave:Biological sciences
Natural sciences
Neuroscience
Pharmacology
Physiology
Descripción
Sumario:The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions. We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis. Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.

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