N-乙酰半胱氨酸可能对帕金森病中的多巴胺能神经元起到支持作用：初步临床及细胞系数据
N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data.
作者信息
Monti Daniel A, Zabrecky George, Kremens Daniel, Liang Tsao-Wei, Wintering Nancy A, Cai Jingli, Wei Xiatao, Bazzan Anthony J, Zhong Li, Bowen Brendan, Intenzo Charles M, Iacovitti Lorraine, Newberg Andrew B
机构信息
Myrna Brind Center of Integrative Medicine, Thomas Jefferson University, Philadelphia, PA, United States of America.
Movement Disorders Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States of America.
出版信息
PLoS One. 2016 Jun 16;11(6):e0157602. doi: 10.1371/journal.pone.0157602. eCollection 2016.
BACKGOUND
The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson's disease (PD).
METHODS
The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson's Disease Rating Scale (UPDRS) to measure clinical symptoms.
RESULTS
The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p<0.05 for all values) in the PD group treated with NAC, and no measurable changes in the control group. UPDRS scores were also significantly improved in the NAC group (mean improvement of 12.9%, p = 0.01).
CONCLUSIONS
The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02445651.
背景
本研究旨在评估N-乙酰半胱氨酸（NAC）对帕金森病（PD）的生物学和临床影响。
方法
这项初步研究的总体目标是，采用体外和体内方法，获取关于NAC在PD中潜在保护特性的更多数据。在准备临床研究时，我们用人胚胎干细胞（hESC）衍生的中脑多巴胺（mDA）神经元进行了细胞组织培养研究，用鱼藤酮作为PD模型对这些神经元进行处理。细胞组织培养的主要结果是在神经毒素鱼藤酮损伤后存活的细胞数量。在临床研究中，患者继续接受标准治疗，并被随机分为两组，一组每天接受NAC治疗，另一组作为候补对照。在接受NAC治疗3个月前后，用DaTscan测量多巴胺转运体（DAT）结合情况，并用统一帕金森病评定量表（UPDRS）测量临床症状，对患者进行评估。
结果
细胞系研究表明，与未使用NAC相比，暴露于NAC后，暴露于鱼藤酮的mDA神经元存活数量显著增加，这与之前观察到的NAC的保护作用一致。临床研究表明，接受NAC治疗的PD组尾状核和壳核中的DAT结合显著增加（平均增加范围为4.4%至7.8%；所有值p<0.05），而对照组没有可测量的变化。NAC组的UPDRS评分也显著改善（平均改善12.9%，p = 0.01）。
结论
这项初步研究的结果首次证明了NAC对PD患者多巴胺系统有潜在的直接作用，这一观察结果可能与积极的临床效果相关。有必要进行大规模临床试验，以测试NAC在该人群中的治疗效果，并更好地阐明其作用机制。
试验注册
ClinicalTrials.gov NCT02445651。
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