Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non‐human primates. Issue 2 (29th January 2015)

• Record Type: Journal Article
• Authors: Jackson, Kasey L.; Dayton, Robert D.; Fisher‐Perkins, Jeanne M.; Didier, Peter J.; Baker, Kate C.; Weimer, Maria; Gutierrez, Amparo; Cain, Cooper D.; Mathis, J. Michael; Gitcho, Michael A.; Bunnell, Bruce A.; Klein, Ronald L.
• Is Part Of: Journal of medical primatology. Volume 44:Issue 2(2015)
• Page Start: 66
• Page End: 75
• Publication Date: 2015-01-29
• Subjects: Primates -- Periodicals; Primates -- Diseases -- Periodicals; Medicine, Experimental -- Periodicals; 616.02738
• DOI: 10.1111/jmp.12162
• Languages: English
• ISSNs: 0047-2565

Abstract

<abstract abstract-type="main" id="jmp12162-abs-0001"> <title>Abstract</title> <sec id="jmp12162-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="jmp12162-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="jmp12162-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="jmp12162-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>