挪威豪克兰大学医院Charalampos Tzoulis研究组开展了NADPARK研究，即在帕金森病人中补充烟酰胺核苷的随机I期临床试验。该研究于2022年3月1日发表于国际学术期刊《细胞-代谢》杂志。
研究人员开展了一项双盲I期临床试验，以确定通过口服烟酰胺核苷(NR)来补充烟酰胺腺嘌呤二核苷酸 (NAD) 的补充疗法是否安全、可增加脑NAD水平并影响帕金森病(PD)人的脑代谢。30名新确诊、未接受过治疗的患者接受了1,000 mg NR或安慰剂治疗30天。NR治疗具有良好的耐受性，并导致NAD水平（通过磷31磁共振波谱测量）和脑脊液中相关代谢物的显著增加。
通过氟18脱氧葡萄糖正电子发射断层扫描测量，结果显示脑NAD水平升高的NR接受者表现出脑代谢改变，这与轻度临床改善有关。NR增强了NAD代谢并诱导与血细胞和/或骨骼肌中线粒体、溶酶体和蛋白酶体功能相关的基因转录上调。
此外，NR降低了血清和脑脊液中炎性细胞因子的水平。该研究结果提示将NR作为PD潜在神经保护疗法值得进行更大规模的临床实验。
附：英文原文
Title: The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease
Author: Brage Brakedal, Christian Dlle, Frank Riemer, Yilong Ma, Gonzalo S. Nido, Geir Olve Skeie, Alexander R. Craven, Thomas Schwarzlmüller, Njl Brekke, Joseph Diab, Lars Sverkeli, Vivian Skjeie, Kristin Varhaug, Ole-Bjrn Tysnes, Shichun Peng, Kristoffer Haugarvoll, Mathias Ziegler, Renate Grüner, David Eidelberg, Charalampos Tzoulis
Issue&Volume: 2022/03/01
Abstract: We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson’s disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels—measured by 31phosphorous magnetic resonance spectroscopy—and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.
DOI: 10.1016/j.cmet.2022.02.001
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00045-6
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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本期文章：《细胞—代谢》：Online/在线发表
