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Neurodegener Dis ; 15(4): 233-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26113413

RESUMO

BACKGROUND/AIM: The sporadic form of the disease affects the majority of amyotrophic lateral sclerosis (ALS) patients. The role of glutamate (Glu) excitotoxicity in ALS has been extensively documented and remains one of the prominent hypotheses of ALS pathogenesis. In light of this evidence, the availability of a method to remove excess Glu from brain and spinal cord extracellular fluids without the need to deliver drugs across the blood-brain barrier and with minimal or no adverse effects may provide a major therapeutic asset, which is the primary aim of this study. METHODS: The therapeutic efficacy of the combined treatment with recombinant Glu-oxaloacetate-transaminase (rGOT) and its co-factor oxaloacetic acid (OxAc) has been tested in an animal model of sporadic ALS. RESULTS: We found that OxAc/rGOT treatment provides significant neuroprotection to spinal cord motor neurons. It also slows down the development of motor weakness and prolongs survival. CONCLUSION: In this study we bring evidence that the administration of Glu scavengers to rats with sporadic ALS inhibited the massive death of spinal cord motor neurons, slowed the onset of motor weakness and prolonged survival. This treatment may be of high clinical significance for the future treatment of chronic neurodegenerative diseases.


Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Aspartato Aminotransferases/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Ácido Oxaloacético/administração & dosagem , Animais , Aspartato Aminotransferases/farmacocinética , Modelos Animais de Doenças , Quimioterapia Combinada , Estimativa de Kaplan-Meier , Masculino , Atividade Motora/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Fármacos Neuroprotetores/farmacocinética , Ácido Oxaloacético/farmacocinética , Ratos , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Teste de Desempenho do Rota-Rod , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia
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