Division of Clinical Pharmacology and Toxicology, Department of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA.
Dev Neurosci. 2011;33(5):414-27. doi: 10.1159/000330861. Epub 2011 Sep 2.
Down syndrome (DS) is the phenotypic consequence of trisomy 21 and is the most common genetically defined cause of intellectual disability. The most complete, widely available, and well-studied animal model of DS is the Ts65Dn mouse. Recent preclinical successes in rescuing learning and memory deficits in Ts65Dn mice are legitimate causes for optimism that pharmacotherapies for cognitive deficits in DS might be within reach. This article provides a snapshot of potential pharmacotherapies for DS, with emphasis on our recent results showing that the N-methyl-D-aspartate receptor antagonist memantine can reverse learning and memory deficits in Ts65Dn mice. Because memantine has already been approved for the therapy of Alzheimer's dementia, we have been able to very rapidly translate these results into human research and are currently conducting a 16-week, randomized, double-blind, placebo-controlled evaluation of the efficacy, tolerability and safety of memantine hydrochloride on enhancing the cognitive abilities of young adults with DS. The design and current status of this clinical trial will be discussed, which will be followed by some speculation on the potential impact of this and future clinical trials in the field of DS.
唐氏综合征（DS）是 21 三体的表型后果，也是智力障碍最常见的遗传定义原因。最完整、应用最广泛、研究最充分的 DS 动物模型是 Ts65Dn 小鼠。最近在 Ts65Dn 小鼠中恢复学习和记忆缺陷的临床前成功，为治疗 DS 认知缺陷的药物治疗可能即将实现提供了合理的乐观理由。本文提供了唐氏综合征潜在药物治疗的概述，重点介绍了我们最近的研究结果，表明 N-甲基-D-天冬氨酸受体拮抗剂美金刚可逆转 Ts65Dn 小鼠的学习和记忆缺陷。由于美金刚已被批准用于治疗阿尔茨海默病痴呆症，我们能够非常迅速地将这些结果转化为人类研究，并正在对盐酸美金刚增强唐氏综合征年轻成年人认知能力的疗效、耐受性和安全性进行为期 16 周、随机、双盲、安慰剂对照评估。将讨论该临床试验的设计和现状，随后对该领域中美金刚和未来临床试验的潜在影响进行一些推测。
