title: Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates.
abstract: BACKGROUND
  Most amyotrophic lateral sclerosis (ALS) research has focused on mice, but there are distinct differences in the functional neuroanatomy of the corticospinal pathway in primates vs. rodents. A non-human primate model may be more sensitive and more predictive for therapeutic efficacy.
  
  
  METHODS
  Rhesus macaques received recombinant adeno-associated virus (AAV9) encoding either the ALS-related pathological protein TDP-43 or a green fluorescent protein (GFP) control by intravenous administration. Motor function and electromyography were assessed over a nine-month expression interval followed by post-mortem analyses.
  
  
  RESULTS
  Recombinant TDP-43 or GFP was stably expressed long term. Although the TDP-43 subjects did not manifest severe paralysis and atrophy, there were trends of a partial disease state in the TDP-43 subjects relative to the control.
  
  
  CONCLUSIONS
  These data indicate that a higher gene vector dose will likely be necessary for more robust effects, yet augur that a relevant primate model is feasible.
authors: Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University, Shreveport, LA, USA.
authors: Kasey L
authors: KL
authors: Jackson
authors: Robert D
authors: RD
authors: Dayton
authors: Jeanne M
authors: JM
authors: Fisher-Perkins
authors: Peter J
authors: PJ
authors: Didier
authors: Kate C
authors: KC
authors: Baker
authors: Maria
authors: M
authors: Weimer
authors: Amparo
authors: A
authors: Gutierrez
authors: Cooper D
authors: CD
authors: Cain
authors: J Michael
authors: JM
authors: Mathis
authors: Michael A
authors: MA
authors: Gitcho
authors: Bruce A
authors: BA
authors: Bunnell
authors: Ronald L
authors: RL
authors: Klein
mesh_terms: D061605:Administration, Intravenous; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004576:Electromyography; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000008:administration & dosage; D006801:Humans; D008253:Macaca mulatta; D009043:Motor Activity; D011994:Recombinant Proteins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; C485192:green fluorescent protein, Aequorea victoria; D049452:Green Fluorescent Proteins
keywords: TDP-43; adeno-associated virus; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; gene therapy; gene transfer
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