Combined Treatment of an Amyotrophic Lateral Sclerosis Rat Model with Recombinant GOT1 and Oxaloacetic Acid: A Novel Neuroprotective Treatment

Angela Ruban, Katayun Cohen-Kashi Malina, Itzik Cooper, Nadine Graubardt, Leonid Babakin, Ghil Jona, Vivian I. Teichberg

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalNeurodegenerative Diseases
Volume15
Issue number4
DOIs
StatePublished - 20 Aug 2015
Externally publishedYes

Keywords

  • Blood glutamate scavenger
  • Excitotoxicity
  • Glutamate
  • Neuroprotection
  • Sporadic amyotrophic lateral sclerosis

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