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, James Michael Mathis, Michael A. Gitcho, Bruce A. Bunnell, Ronald L. Klein

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalJournal of Medical Primatology
Volume44
Issue number2
DOIs
StatePublished - 1 Apr 2015

Fingerprint

Amyotrophic Lateral Sclerosis
green fluorescent protein
Dependovirus
Primates
animal models
Green Fluorescent Proteins
electromyography
paralysis
Macaca mulatta
atrophy
intravenous injection
Genes
Neuroanatomy
rodents
genes
Electromyography
Paralysis
Intravenous Administration
therapeutics
Atrophy

Keywords

  • 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., ... 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. https://doi.org/10.1111/jmp.12162
Jackson, Kasey L. ; Dayton, Robert D. ; Fisher-Perkins, Jeanne M. ; Didier, Peter J. ; Baker, Kate C. ; Weimer, Maria ; Gutierrez, Amparo ; Cain, Cooper D. ; Mathis, James Michael ; Gitcho, Michael A. ; Bunnell, Bruce A. ; Klein, Ronald L. / Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates. In: Journal of Medical Primatology. 2015 ; Vol. 44, No. 2. pp. 66-75.
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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.",
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Jackson, KL, Dayton, RD, Fisher-Perkins, JM, Didier, PJ, Baker, KC, Weimer, M, Gutierrez, A, Cain, CD, Mathis, JM, Gitcho, MA, Bunnell, BA & Klein, RL 2015, 'Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates', Journal of Medical Primatology, vol. 44, no. 2, pp. 66-75. https://doi.org/10.1111/jmp.12162

Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates. / Jackson, Kasey L.; Dayton, Robert D.; Fisher-Perkins, Jeanne M.; Didier, Peter J.; Baker, Kate C.; Weimer, Maria; Gutierrez, Amparo; Cain, Cooper D.; Mathis, James Michael; Gitcho, Michael A.; Bunnell, Bruce A.; Klein, Ronald L.

In: Journal of Medical Primatology, Vol. 44, No. 2, 01.04.2015, p. 66-75.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates

AU - Jackson, Kasey L.

AU - Dayton, Robert D.

AU - Fisher-Perkins, Jeanne M.

AU - Didier, Peter J.

AU - Baker, Kate C.

AU - Weimer, Maria

AU - Gutierrez, Amparo

AU - Cain, Cooper D.

AU - Mathis, James Michael

AU - Gitcho, Michael A.

AU - Bunnell, Bruce A.

AU - Klein, Ronald L.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

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M3 - Article

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JF - Journal of Medical Primatology

SN - 0047-2565

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