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

Kasey L. Jackson, Robert D. Dayton, Jeanne M. Fisher-Perkins, Peter J. Didier, Kate C. Baker, Maria Weimer, Amparo Gutierrez, Cooper D. Cain, J. Michael Mathis, Michael A. Gitcho, Bruce A. Bunnell, Ronald L. Klein

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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.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalJournal of Medical Primatology
Issue number2
StatePublished - 1 Apr 2015



  • Adeno-associated virus
  • Amyotrophic lateral sclerosis
  • Frontotemporal lobar degeneration
  • Gene therapy
  • Gene transfer
  • TDP-43

Cite this

Jackson, K. L., Dayton, R. D., Fisher-Perkins, J. M., Didier, P. J., Baker, K. C., Weimer, M., Gutierrez, A., Cain, C. D., Michael Mathis, J., Gitcho, M. A., Bunnell, B. A., & Klein, R. L. (2015). Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates. Journal of Medical Primatology, 44(2), 66-75.