Becker Robert E, Greig Nigel H
Aristea Translational Medicine Corp., Freeport, 7123 Pinebrook Road, Park City, UT 84098, USA.
Curr Alzheimer Res. 2014 Mar;11(3):215-20. doi: 10.2174/156720501103140329210642.
A surfeit of errors and an absence of sufficiently rigorous neuroscience theory have led to failures of neuroscience drug developments and to less effective patient care. Alzheimer's disease (AD) requires systematic grounding of drug developments with mechanistic explanations to replace current trial and error approaches to the development of potential drug products. We foresee the need for regulatory revisions that will provide better balanced supports for advancing the AD scientific knowledge required to more effectively develop clinically useful drugs and for provisions to patients of drug candidates soundly predicted, based on documented effects on AD neuropathologies and safety, to slow or arrest the progression of persons at-risk to AD dementia. We propose that investigators and regulators focus AD clinical research on understanding the inductions of reversible and irreversible neuropathologies and their roles in generating clinical dementia. In support of this, we foresee the need for regulatory changes to create a vehicle for these clinical studies; for example, conditional drug approvals based on drug induced neuropathological changes.
大量的错误以及缺乏足够严谨的神经科学理论，导致神经科学药物研发失败，患者护理效果欠佳。阿尔茨海默病（AD）的药物研发需要基于机制解释进行系统的基础研究，以取代当前开发潜在药物产品的试错方法。我们预见到需要进行监管修订，以便为推进AD科学知识提供更平衡的支持，从而更有效地开发临床有用的药物，并为患者提供基于对AD神经病理学和安全性的记录效应而可靠预测的候选药物，以减缓或阻止有AD痴呆风险人群的病情进展。我们建议研究人员和监管机构将AD临床研究重点放在理解可逆和不可逆神经病理学的诱导因素及其在引发临床痴呆中的作用上。为此，我们预见到需要进行监管变革，以创建开展这些临床研究的途径；例如，基于药物诱导的神经病理学变化给予有条件的药物批准。
