The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes.
The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes.
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DOI：
10.1016/j.neuropharm.2016.03.021
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发表时间：
2017-07-01
影响因子：
4.7
通讯作者：
Kaczmarek LK
中科院分区：
文献类型：
--
作者：
Gribkoff VK;Kaczmarek LK
生物医学研究的一个重要目标是将基础研究成果转化为有用的医学进步。在神经药理学领域，这需要了解疾病机制以及药物和其他化合物对神经元功能的影响。我们希望这些信息将导致新的或改进的治疗中枢神经系统疾病。尽管我们对中枢神经系统的结构和功能的理解取得了很大进展，但许多中枢神经系统疾病的新药发现及其临床开发一直存在问题。因此，CNS药物发现和开发计划在过去十年中受到了显着的削减和取消。虽然最近对CNS靶点的兴趣有所恢复，但制药和生物技术行业过去优先事项的这些变化反映了几个有据可查的现实。CNS药物通常在临床前和临床上的失败率高于非CNS药物，并且在某些领域，例如主要的神经退行性疾病，疾病改善治疗的临床失败率为100%。CNS药物的开发时间对于那些已批准的药物来说明显更长，并且开发后监管审查更长。在这篇导言中，我们回顾了失败的一些原因，描述了科学和技术的现实，一些独特的CNS，促成了这一点。我们将专注于影响数百万人的主要神经退行性疾病，吸引了大部分头条新闻，但却见证了最少的成功。我们将提出一些改变，当与本特别卷的其余部分讨论的方法相结合时，可能会改善未来CNS靶向药物发现和开发工作的结果。
An important goal of biomedical research is to translate basic research findings into useful medical advances. In the field of neuropharmacology this requires understanding disease mechanisms as well as the effects of drugs and other compounds on neuronal function. Our hope is that this information will result in new or improved treatment for CNS disease. Despite great progress in our understanding of the structure and functions of the CNS, the discovery of new drugs and their clinical development for many CNS disorders has been problematic. As a result, CNS drug discovery and development programs have been subjected to significant cutbacks and eliminations over the last decade. While there has been recent resurgence of interest in CNS targets, these past changes in priority of the pharmaceutical and biotech industries reflect several well-documented realities. CNS drugs in general have higher failure rates than non-CNS drugs, both preclinically and clinically, and in some areas, such as the major neurodegenerative diseases, the clinical failure rate for disease-modifying treatments has been 100%. The development times for CNS drugs are significantly longer for those drugs that are approved, and post-development regulatory review is longer. In this introduction we review some of the reasons for failure, delineating both scientific and technical realities, some unique to the CNS, that have contributed to this. We will focus on major neurodegenerative disorders, which affect millions, attract most of the headlines, and yet have witnessed the fewest successes. We will suggest some changes that, when coupled with the approaches discussed in the rest of this special volume, may improve outcomes in future CNS-targeted drug discovery and development efforts.
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影响因子：
8.2
作者：
Branchi, I;Bichler, Z;Ricceri, L
通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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