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

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

Author information

1
Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University, Shreveport, LA, USA.

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.

KEYWORDS:

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

PMID:
25639184
PMCID:
PMC4385002
DOI:
10.1111/jmp.12162
[Indexed for MEDLINE]
Free PMC Article

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