Therapeutic effect of peripheral administration of an anti-prion protein antibody on mice infected with prions
Therapeutic effect of peripheral administration of an anti-prion protein antibody on mice infected with prions
复制标题
抗朊病毒蛋白抗体外周给药对朊病毒感染小鼠的治疗作用
DOI：
10.1111/j.1348-0421.12037
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
N.
中科院分区：
文献类型：
--
作者：
Ohsawa;N.
一般认为朊病毒病的有效治疗需要抑制朊病毒的增殖，保护神经组织，促进变性神经组织的功能恢复。此外，即使在疾病临床发作后给予并通过外周途径给药，此类治疗也应有效。在本研究中，检查了外周给予抗PrP抗体对朊病毒感染小鼠疾病进展的影响。在临床发作时（接种钱德勒朊病毒株后120天），通过朊病毒感染小鼠的尾静脉给予mAb 31 C6，并评估该mAb在脑中的分布及其对小鼠存活的影响。抗体分布到感染小鼠的小脑和丘脑，超过一半的小鼠比给予阴性对照mAb的小鼠存活更长时间。mAb 31C6给药小鼠的PrPScin水平低于阴性对照mAb给药小鼠，并且mAb 31C6分布良好的小脑神经病理学病变进展似乎有所缓解。这些结果表明，通过外周途径给予抗PrP mAb是治疗朊病毒疾病的候选药物。
It is generally thought that effective treatments for prion diseases need to inhibit prion propagation, protect neuronal tissues and promote functional recovery of degenerated nerve tissues. In addition, such treatments should be effective even when given after clinical onset of the disease and administered via a peripheral route. In this study, the effect of peripheral administration of an anti‐PrP antibody on disease progression in prion‐infected mice was examined. mAb 31C6 was administered via the tail veins of prion‐infected mice at the time of clinical onset (120 days post‐inoculation with the Chandler prion strain) and the distribution of this mAb in the brain and its effect on mouse survival assessed. The antibody was distributed to the cerebellums and thalami of the infected mice and more than half these mice survived longer than mice that had been given a negative control mAb. The level of PrPScin the mAb 31C6‐treated mice was lower than that in mice treated with the negative control mAb and progression of neuropathological lesions in the cerebellum, where the mAb 31C6 was well distributed, appeared to be mitigated. These results suggest that administration of an anti‐PrP mAb through a peripheral route is a candidate for the treatment of prion diseases.