title: Combined Treatment of an Amyotrophic Lateral Sclerosis Rat Model with Recombinant GOT1 and Oxaloacetic Acid: A Novel Neuroprotective Treatment.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Angela
authors.initials: A
authors.lastname: Ruban
authors.forename: Katayun Cohen-Kashi
authors.initials: KC
authors.lastname: Malina
authors.forename: Itzik
authors.initials: I
authors.lastname: Cooper
authors.forename: Nadine
authors.initials: N
authors.lastname: Graubardt
authors.forename: Leonid
authors.initials: L
authors.lastname: Babakin
authors.forename: Ghil
authors.initials: G
authors.lastname: Jona
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Teichberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D053208:Kaplan-Meier Estimate; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D062907:Oxaloacetic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D045442:Rotarod Performance Test; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D062907:Oxaloacetic Acid; D001219:Aspartate Aminotransferases