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Challenges and Opportunities for Translation of Therapies to Improve Cognition in Down Syndrome.
Trends in Molecular Medicine ( IF 13.6 ) Pub Date : 2019-11-07 , DOI: 10.1016/j.molmed.2019.10.001
Sarah E Lee 1 , Monica Duran-Martinez 1 , Sabina Khantsis 1 , Diana W Bianchi 2 , Faycal Guedj 1
Affiliation  

While preclinical studies have reported improvement of behavioral deficits in the Ts65Dn mouse model of Down syndrome (DS), translation to human clinical trials to improve cognition in individuals with DS has had a poor success record. Timing of the intervention, choice of animal models, strategy for drug selection, and lack of translational endpoints between animals and humans contributed to prior failures of human clinical trials. Here, we focus on in vitro cell models from humans with DS to identify the molecular mechanisms underlying the brain phenotype associated with DS. We emphasize the importance of using these cell models to screen for therapeutic molecules, followed by validating them in the most suitable animal models prior to initiating human clinical trials.

中文翻译:

翻译疗法以改善唐氏综合症认知的挑战和机遇。

虽然临床前研究已经报道了唐氏综合症(DS)的Ts65Dn小鼠模型中行为缺陷的改善,但为改善DS个体的认知而进行的人类临床试验翻译却取得了较差的成功记录。干预的时机,动物模型的选择,药物选择的策略以及动物与人之间缺乏翻译终点的原因导致了先前人类临床试验的失败。在这里,我们重点研究具有DS的人类的体外细胞模型,以确定与DS相关的脑表型的潜在分子机制。我们强调使用这些细胞模型筛选治疗性分子的重要性,然后在启动人类临床试验之前在最合适的动物模型中对其进行验证。
更新日期:2019-11-07
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