来源 | 科研大匠综合自Nature/科研大匠之前推文

编辑 | 学术君

2020年7月6日,现任首都医科大学校长、北大麦戈文研究所创始所长饶毅首次以期刊编辑委员会的成员身份在Cell Research 在线发表题为“Omission of previous publications by an author should be corrected”(作者遗漏了之前的研究,应予以更正)的文章,在文章中,饶毅提醒读者:耿美玉团队已经发表了12篇关于GV971或与GV971相关的论文(其中7篇原创研究,5篇评论文章),但耿美玉团队2019年10月发表的关于GV-971的研究对于之前发表的这12篇论文却一篇也没有引用。同时,饶毅还表达了对该研究“可信性”的“潜在担忧”。称“我从来没有遇到过一种药物有这么多的靶点可以治疗或缓解一种疾病。”

2019年9月6日,中国科学院上海药物所耿美玉团队的一篇研究登上了被称为“国刊之光”的Cell Research(今年IF首次突破20)封面。研究题为“Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression”封面用一句话概括了GV-971的原理:通过重建肠道菌群,来治疗阿尔茨海默病 (AD)。

基于该研究及耿美玉团队之前相关研究,团队研发出了被称为中国原创,全球首个治疗阿尔茨海默病新药:九期一”,目前,该药已经上市,定价895元。同时,该药已经获FDA批准,可在美国直接进行三期临床试验。详见:

耿美玉和“九期一” 图源网络

中国原创,全球首个,一文梳理被称为“国际巨头研发坟场”的治疗阿尔茨海默病获准上市新药研发进程来了!中国原创“神药”定价895元,耿美玉团队回应五大质疑厉害了!“饱受争议”的我国原创抗痴呆药GV-971获FDA批准!可在美国直接进行三期临床试验

但,质疑之声四起。

2019年11月28日,饶毅在写给国自然基金委的一封举报信中,曾实名举报耿美玉造假,称该研究“不造假是不可能的”。见:

首都医科大学校长饶毅实名举报李红良、耿美玉、裴钢学术造假

此次,饶毅再次以Cell Research 编辑委员会委员身份直接在期刊发文对该研究发出质疑,文章中译文及英文原文如下:

左:饶毅 右:耿美玉

作为《细胞研究》的编委会成员,我写信是为了向《细胞研究》2019年10月号发表的Wang et al.1关于GV971的论文的读者提供必要的信息。

值得注意的是,该论文的通讯作者耿美玉博士此前已经发表了12篇关于GV971或与GV971密切相关的论文,包括体内和体外研究。由于这些论文在Wang et al.1中没有一篇被引用,所以在这里列出来以便让读者知晓。其中7篇为GV971,2,3,4,5,6,7,8 的原始研究论文,其余为评论或相关论文。9,10,11,12,13

总而言之,耿美玉博士先前论文声称GV971可以治疗帕金森病动物模型2,GV971可以直接绑定到β淀粉样蛋白肽,4,9,GV971可以保护神经元免受β淀粉样蛋白的毒性,4,5,GV971可以改善记忆丧失引起的β淀粉样蛋白肽注入大脑,6,GV971可以直接抑制过氧化氢诱导神经元死亡,3,GV971可以减弱莨菪碱诱导大鼠记忆障碍,3 GV971可以作用于星形胶质细胞在vitro8 GV971可以与神经元内的蛋白质结合,7。虽然这些作用直接作用于A肽类,或直接作用于神经系统内的神经元或胶质细胞,但Wang等人现在声称GV 971通过调节肠道微生物和炎症间接作用于阿尔茨海默病的动物模型。这些效应在药物靶点、有效位点的位置和治疗机制方面是如此显著地不同,以至于引起了对可信性的潜在担忧。读者不应忽视的一点是,尽管通常来说存在不同的靶标意味着副作用,但作者声称,GV971的所有靶标和作用都有助于缓解阿尔茨海默病。

在我自己对生物医学研究历史的研究中,从中国的生物医学研究(包括但不限于抗疟疾药物青蒿素和抗白血病药物三氧化二砷的发现,14)到世界各地的生物医学研究,15 ,我从来没有遇到过一种药物有这么多的靶点可以治疗或缓解一种疾病。

As a member of the Editorial Board of Cell Research, I am writing to provide essential information to readers of the Wang et al.1 paper on GV971 published in the October 2019 issue of Cell Research.

It should be noted that the corresponding author of the paper, Dr Meiyu Geng, has previously published 12 papers on or closely related to GV971, including both in vitro and in vivo studies. Because not a single one of these papers was cited in Wang et al.,1 they are listed here so that the readers would be aware of them. Seven papers are original research papers on GV971,2,3,4,5,6,7,8 while others are reviews or related papers.9,10,11,12,13

To summarize, previous papers by Dr Geng have claimed that GV971 can treat Parkinson’s disease in animal models,2 that GV971 can directly bind to amyloid β peptides,4,9 that GV971 can protect neurons from amyloid β toxicity,4,5 that GV971 can ameliorate memory loss caused by amyloid β peptide injection into the brain,6 that GV971 can inhibit H2O2 induced neuronal death directly,3 that GV971 can attenuate scopolamine induced memory impairment in rats,3 that GV971 can act on astrocytes in vitro8 and that GV971 can bind to proteins inside neurons.7 While those effects were directly on the Aβ peptide, or directly on neurons or glial cells, all inside the nervous system, Wang et al.1 now claim that GV 971 works on Alzheimer’s animal model indirectly through regulating gut microbiomes and inflammation. These effects are so strikingly different with regard to drug target(s), location of effective sites and therapeutic mechanisms that they raised a potential concern of credibility. It should not escape the attention of readers that, while usually the existence of diverse targets means side effects, the authors claim all targets and effects of GV971 are helping to alleviate the Alzheimer’s disease.

In my own study of the history of biomedical research, ranging from that in China which includes but is not limited to, the discovery of the antimalaria drug artemisinin and the anti-leukemia drug arsenic trioxide,14 to that in the rest of the world,15 I have never come across a single drug with so many targets for curing or alleviating one disease.

相关论文:

1. Wang, X. et al. Cell Res. 29, 787–803 (2019).

2. Dong, X., Geng, M., Guang, H. & Xie, J. Chin. J. Mar. Drugs 9, 9–12 (2003). (in Chinese).

3. Fan, Y. et al. Neurosci. Lett. 374, 222–226 (2005).

4. Hu, J. et al. J. Pharmacol. Sci. 95, 248–255 (2004).

5. Jiang, R. et al. Acta Pharmacol. Sin. 34, 1585–1591 (2013).

6. Kong, L. et al. Yao Xue Xue Bao 40, 1105–1109 (2005). (in Chinese).

7. Liu, M., Nie, Q., Xin, X. & Geng, M. Chin. J. Ocenol. Limnol. 26, 394–399 (2008).

8. Wang, S., Li, J., Xia, W. & Geng, M. Neurol. Res. 29, 96–102 (2007).

9. Geng, M. Zhongguo Yao Li Tong Xun 24, 8 (2007). (in Chinese).

10. Guo, X., Geng, M. & Du, D. Biochem. Genet. 43, 175–187 (2005).

11. Hu, J. F., Geng, M. Y. & Zhang, J. T. Zhongguo Yao Li Xue Tong Bao 19, 12–16 (2003). (in Chinese).

12. Nie, Q., Du, X. & Geng, M. Acta Pharmacol. Sin. 32, 545–551 (2011).

13. Wang, S., Li, J. & Geng, M. Sheng Li Ke Xue Jin Zhan 36, 67–70 (2005). (in Chinese).

静待后续。

参考文献:

https://www.nature.com/articles/s41422-020-0344-3

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