Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates.
Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates.
复制标题
DOI：
10.1111/jmp.12162
复制
发表时间：
2015-04
影响因子：
0.7
通讯作者：
Klein RL
中科院分区：
文献类型：
--
作者：
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
大多数肌萎缩侧索硬化症（ALS）的研究都集中在小鼠身上，但灵长类动物与啮齿类动物的皮质脊髓通路的功能神经解剖学存在明显差异。非人灵长类动物模型可能对治疗功效更敏感且更具预测性。恒河猴通过静脉内给药接受编码ALS相关病理蛋白TDP-43或绿色荧光蛋白（GFP）对照的重组腺相关病毒（AAV 9）。运动功能和肌电图进行了评估，超过9个月的表达间隔，随后进行尸检分析。重组TDP-43或GFP长期稳定表达。尽管TDP-43受试者没有表现出严重的瘫痪和萎缩，但相对于对照，TDP-43受试者中存在部分疾病状态的趋势。这些数据表明，更高的基因载体剂量可能需要更强大的效果，但预示着相关的灵长类动物模型是可行的。
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. 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. 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. 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.
登录
查看更多内容
影响因子：
38.1
作者：
Chen-Plotkin, Alice S.;Lee, Virginia M. -Y.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
5.1
作者：
McCarty, DM;Monahan, PE;Samulski, RJ
通讯作者：
Samulski, RJ
影响因子：
11.2
作者：
England, JD;Bohm, RP;Philipp, MT
通讯作者：
Philipp, MT
影响因子：
4.6
作者：
Dayton RD;Wang DB;Klein RL
通讯作者：
Klein RL