美国威斯康星大学麦迪逊分校Su-Chun Zhang和Marina E. Emborg研究组合作取得最新进展。他们揭示自体移植疗法可减轻帕金森氏病（PD）猴的运动和抑郁行为。相关论文于2021年3月1日发表于《自然-医学》。

他们显示了未施加免疫抑制的2年时间内，接受自体而非同种异体移植的PD猴子表现出从运动和抑郁症状中恢复的过程。这些行为的改善伴随着具有广泛中脑多巴胺（DA）神经元轴突生长的强健移植物，以及在正电子发射断层扫描（PET）中具有强大的DA活性。数学模型揭示了存活的DA神经元数目与PET信号强度之间的相关性，而无论自体移植或同种异体移植都与行为恢复相关，这表明PET和运动行为对于存活DA神经元数目的预测能力。

据介绍，DA神经元的退化是PD发病机理的基础。通过L-DOPA补充DA可减轻运动症状，但不能防止DA神经元的进行性丧失。包括非人类灵长类动物在内的大量实验研究表明，胎儿中脑组织的移植改善了动物的运动症状，这一结果在针对PD1的胎儿组织移植的开放标签和双盲临床试验中得到证实。不幸的是，结果参差不齐，主要是由于未定义和标准化的供体组织。诱导型多能干细胞的产生使PD的标准化和自体移植治疗成为可能。但是，其功效，尤其是灵长类动物的功效尚不清楚。

附：英文原文

Title: Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys

Author: Yunlong Tao, Scott C. Vermilyea, Matthew Zammit, Jianfeng Lu, Miles Olsen, Jeanette M. Metzger, Lin Yao, Yuejun Chen, Sean Phillips, James E. Holden, Viktoriya Bondarenko, Walter F. Block, Todd E. Barnhart, Nancy Schultz-Darken, Kevin Brunner, Heather Simmons, Bradley T. Christian, Marina E. Emborg, Su-Chun Zhang

Issue&Volume: 2021-03-01

Abstract: Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson’s disease (PD). Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons. A large body of experimental studies, including those in nonhuman primates, demonstrates that transplantation of fetal mesencephalic tissues improves motor symptoms in animals, which culminated in open-label and double-blinded clinical trials of fetal tissue transplantation for PD1. Unfortunately, the outcomes are mixed, primarily due to the undefined and unstandardized donor tissues1,2. Generation of induced pluripotent stem cells enables standardized and autologous transplantation therapy for PD. However, its efficacy, especially in primates, remains unclear. Here we show that over a 2-year period without immunosuppression, PD monkeys receiving autologous, but not allogenic, transplantation exhibited recovery from motor and depressive signs. These behavioral improvements were accompanied by robust grafts with extensive DA neuron axon growth as well as strong DA activity in positron emission tomography (PET). Mathematical modeling reveals correlations between the number of surviving DA neurons with PET signal intensity and behavior recovery regardless autologous or allogeneic transplant, suggesting a predictive power of PET and motor behaviors for surviving DA neuron number.

DOI: 10.1038/s41591-021-01257-1

Source: https://www.nature.com/articles/s41591-021-01257-1