State University of New York at Buffalo, 875 Ellicott St., Buffalo, NY, 14203, USA.
CNS Drugs. 2022 Apr;36(4):365-376. doi: 10.1007/s40263-022-00915-3. Epub 2022 Mar 30.
The development of Alzheimer's disease therapeutics has been challenging, with 99% of clinical trials failing to find a significant difference between drug and placebo. While the quest continues for more effective treatments, there is emerging evidence that pharmacogenetic considerations are important factors in regard to metabolism, efficacy, and toxicity of drugs. Currently, there are five US Food and Drug Administration-approved drugs for the treatment of Alzheimer's disease; three acetylcholinesterase inhibitors, memantine, and aducanumab. Introducing a limited genetic panel consisting of APOE4, CYP2D610, and BChEK would optimize acetylcholinesterase inhibitor therapy, facilitate immunotherapy risk assessment, and inform an amyloid-related imaging abnormality surveillance schedule. In view of the genetic heterogeneity of Alzheimer's disease identified in genome-wide association studies, pharmacogenetics is expected to play an increasing role in mechanism-specific treatment strategies and personalized medicine.
阿尔茨海默病治疗药物的研发一直具有挑战性，99%的临床试验未能发现药物与安慰剂之间的显著差异。虽然人们仍在继续寻找更有效的治疗方法，但有证据表明，药物代谢、疗效和毒性的药物遗传学考虑是重要因素。目前，有 5 种美国食品和药物管理局批准的用于治疗阿尔茨海默病的药物；三种乙酰胆碱酯酶抑制剂、美金刚和 aducanumab。引入一个有限的基因检测面板，包括 APOE4、CYP2D610 和 BChEK，将优化乙酰胆碱酯酶抑制剂治疗，促进免疫治疗风险评估，并为淀粉样蛋白相关成像异常监测计划提供信息。鉴于全基因组关联研究中确定的阿尔茨海默病的遗传异质性，药物遗传学预计将在针对特定机制的治疗策略和个性化医学中发挥越来越重要的作用。
