Sramek J J, Cutler N R
California Clinical Trials, 8500 Wilshire Boulevard, 7th Floor, Beverly Hills, CA 90211, USA. jsramek@cctrials:com
Expert Opin Investig Drugs. 2000 Apr;9(4):899-915. doi: 10.1517/13543784.9.4.899.
Researchers have sought to understand the underlying pathophysiology of Alzheimer's disease (AD) ever since Dr A Alzheimer first described the condition in 1907. Unfortunately however, until recently, they have done so with limited success. This lack of clarity has deterred advancements in therapeutic drug research beyond all but the purely symptomatic treatment relief currently available. However, through spatio-temporal analysis of the two types of cerebral lesions that characterise the disorder (senile plaques and neurofibrillary tangles) and the compilation of genetic data concerning familial AD, there now exists the foundation for a more comprehensive understanding of the disease. Although symptomatic cholinergic strategies have beneficial effects, their benefits are modest and current research has turned to the development of other promising strategies, including oestrogen replacement, anti-inflammatory agents, free radical scavengers, anti-oxidants and monoamine oxidase-B (MAO-B) inhibitors. Many of these strategies may have some merit, however further analysis and structured research are necessary before a definitive decision can be made about their efficacy and possible role in AD therapy. Strategies that are directed at halting the underlying biochemical changes in AD are nearing clinical testing and offer the promise for meaningful therapeutic outcomes.
自1907年阿洛伊斯·阿尔茨海默医生首次描述阿尔茨海默病(AD)以来,研究人员一直试图了解其潜在的病理生理学。然而不幸的是,直到最近,他们的进展有限。这种不明确阻碍了治疗药物研究的进展,除了目前可用的纯粹对症治疗缓解之外。然而,通过对该疾病特征性的两种脑损伤(老年斑和神经原纤维缠结)进行时空分析以及汇编有关家族性AD的遗传数据,现在有了更全面了解该疾病的基础。尽管对症胆碱能策略有有益效果,但效果有限,目前的研究已转向开发其他有前景的策略,包括雌激素替代、抗炎药、自由基清除剂、抗氧化剂和单胺氧化酶-B(MAO-B)抑制剂。这些策略中的许多可能有一定价值,然而在就它们在AD治疗中的疗效和可能作用做出明确决定之前,还需要进一步分析和结构化研究。针对阻止AD潜在生化变化的策略已接近临床试验阶段,并有望带来有意义的治疗结果。