From chemical to drug: neurodegeneration drug screening and the ethics of clinical trials
From chemical to drug: neurodegeneration drug screening and the ethics of clinical trials
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DOI：
10.1038/nn931
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发表时间：
2002-11-01
影响因子：
25
通讯作者：
Ravina, B
中科院分区：
文献类型：
--
作者：
Heemskerk, J;Tobin, AJ;Ravina, B
[doi: 10.1038/nn931]可疑的神经退行性变机制，如蛋白质构象、蛋白质聚集或RNA剪接的改变1,2，而其他目标是“现象”的，如防止培养或无脊椎神经系统中的神经元细胞死亡4。发现的化合物为有神经退行性疾病遗传风险或已经患有此类疾病的人提供了有益的希望。具有讽刺意味的是，候选药物的激增往往带来更多的焦虑而不是兴奋。面对体外筛选的积极结果，研究人员陷入了一个困难的科学和伦理问题：在提出临床试验之前，他们需要知道多少？科学家们通常有一种假设，即在药物在病人身上试用之前，进一步的实验必须消除所有的怀疑。不幸的是，强加这种条件几乎肯定会阻止任何药物进入诊所。
doi: 10.1038/nn931 suspected mechanisms of neurodegeneration, such as changes in protein conformation1, protein aggregation4 or RNA splicing2, 4, whereas other targets were ‘phenomenological’, such as preventing the death of neuronal cells in culture or in an invertebrate nervous system4. The compounds identified offer promise of benefit to people at genetic risk for neurodegenerative disorders or already suffering from such a disease. Ironically, the proliferation of candidate drugs has often brought more angst than excitement. Faced with a positive result from an in vitro screen, researchers become entangled in a difficult scientific and ethical question: how much do they need to know before proposing a clinical trial? There is often an assumption among scientists that further experimentation must remove all doubt before a drug is tried in patients. Unfortunately, imposing this condition would almost certainly prevent any drugs from ever reaching the clinic.