Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates

J Med Primatol. 2015 Apr;44(2):66-75. doi: 10.1111/jmp.12162. Epub 2015 Jan 29.


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.

Keywords: TDP-43; adeno-associated virus; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; gene therapy; gene transfer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Amyotrophic Lateral Sclerosis / therapy*
  • Animals
  • DNA-Binding Proteins / administration & dosage
  • DNA-Binding Proteins / genetics*
  • Dependovirus / genetics
  • Disease Models, Animal*
  • Electromyography
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics*
  • Green Fluorescent Proteins / administration & dosage
  • Humans
  • Macaca mulatta*
  • Motor Activity
  • Recombinant Proteins / genetics


  • DNA-Binding Proteins
  • Recombinant Proteins
  • green fluorescent protein, Aequorea victoria
  • Green Fluorescent Proteins