柳叶刀:唐氏综合征治疗“大跃进”,绿茶改善患者认知能力
2016/06/12
科学家于本周二表示,绿茶中的化学物质已被证明能改善唐氏综合征患者的认知能力。经过一年的临床试验,研究人员发现绿茶可提高患者的记忆和行为能力,且试验结束后,该效应还能持续六个月。相关结果发表在《The Lancet Neurology》上。


科学家于本周二表示,绿茶中的化学物质已被证明能改善唐氏综合征患者的认知能力。经过一年的临床试验,研究人员发现绿茶可提高患者的记忆和行为能力,且试验结束后,该效应还能持续六个月。相关结果发表在《The Lancet Neurology》上。

脑部扫描显示,一种称为表没食子儿茶素没食子酸酯(epigallocatechin gallate)改变大脑中神经元之间的连接方式。本研究第一作者,巴塞罗那基因组调控研究中心Mara Dierssen表示,“该研究是首个显示绿茶治疗能改善唐氏综合征患者认知的研究。”然而,她在一份声明中补充道,“该研究结果不应该被解释为治疗,但它或许能作为一种改善唐氏综合征患者生活质量的途径”。此外,未参加该研究的专家也认为该结果令人兴奋,是一项重要的发现。但专家警告称,该结果还需更多的临床试验进行验证。

唐氏综合征是一种最常见的遗传性智力障碍,据世界卫生组织,大约每1000个人中有1个唐氏综合征患者。唐氏综合征也被称为21三体综合征,是由染色体异常(多了一条21号染色体)而导致的疾病。

健康人体通常有23对染色体,包含大约25000个蛋白的编码基因。而唐氏综合征患者额外的拷贝数导致21染色体上的基因过量表达,从而导致认知能力下降和其他健康问题。在早期的小鼠实验中,Dierssen发现抑制DYRK1A基因可改善大脑的功能和发展。

“大跃进”

然而,这种基因疗法对人类而言存在一定的困难,因而研究者们转向了绿茶化合物。在本次试验中,84名唐氏综合征年轻患者被分为两组,第一组给予不含咖啡因包含45%表没食子儿茶素没食子酸酯的绿茶补充物,并每周给予认知训练,第二组给予相同的认知训练,但以等量的安慰剂取代绿茶补充物。

受试者在试验3、6、12月后分别接受认知测试。两组患者在大多数特征上没有太大变化,但在一些记忆模式、回忆能力及适应行为中,绿茶组患者测试分数更高。此外,这些能力随时间推移而改善。

伦敦帝国理工学院神经药理学中心主任David Nutt对该研究评论道,“对唐氏综合征遗传神经生物学的理解为疾病的个性化治疗提供了可能”。巴黎大脑和脊椎研究所唐氏综合征专家Marie-Claude Potier说,“该研究结果是一个质的飞跃,但安全性和有效性有待确认”。然而,另外一些研究者警告说,尽管新研究有一定的重要性,但遗传仍不能说明一切,了解一个人的遗传条件、环境背景以及其他健康问题和受教育问题同样重要。

相关链接:

Down's syndrome 'treated' with green tea: study

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  • Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial

    Background Early cognitive intervention is the only routine therapeutic approach used for amelioration of intellectual deficits in individuals with Down's syndrome, but its effects are limited. We hypothesised that administration of a green tea extract containing epigallocatechin-3-gallate (EGCG) would improve the effects of non-pharmacological cognitive rehabilitation in young adults with Down's syndrome. Methods We enrolled adults (aged 16–34 years) with Down's syndrome from outpatient settings in Catalonia, Spain, with any of the Down's syndrome genetic variations (trisomy 21, partial trisomy, mosaic, or translocation) in a double-blind, placebo-controlled, phase 2, single centre trial (TESDAD). Participants were randomly assigned at the IMIM-Hospital del Mar Medical Research Institute to receive EGCG (9 mg/kg per day) or placebo and cognitive training for 12 months. We followed up participants for 6 months after treatment discontinuation. We randomly assigned participants using random-number tables and balanced allocation by sex and intellectual quotient. Participants, families, and researchers assessing the participants were masked to treatment allocation. The primary endpoint was cognitive improvement assessed by neuropsychologists with a battery of cognitive tests for episodic memory, executive function, and functional measurements. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01699711. Findings The study was done between June 5, 2012, and June 6, 2014. 84 of 87 participants with Down's syndrome were included in the intention-to-treat analysis at 12 months (43 in the EGCG and cognitive training group and 41 in the placebo and cognitive training group). Differences between the groups were not significant on 13 of 15 tests in the TESDAD battery and eight of nine adaptive skills in the Adaptive Behavior Assessment System II (ABAS-II). At 12 months, participants treated with EGCG and cognitive training had significantly higher scores in visual recognition memory (Pattern Recognition Memory test immediate recall, adjusted mean difference: 6·23 percentage points [95% CI 0·31 to 12·14], p=0·039; d 0·4 [0·05 to 0·84]), inhibitory control (Cats and Dogs total score, adjusted mean difference: 0·48 [0·02 to 0·93], p=0·041; d 0·28 [0·19 to 0·74]; Cats and Dogs total response time, adjusted mean difference: −4·58 s [–8·54 to −0·62], p=0·024; d −0·27 [–0·72 to −0·20]), and adaptive behaviour (ABAS-II functional academics score, adjusted mean difference: 5·49 [2·13 to 8·86], p=0·002; d 0·39 [–0·06 to 0·84]). No differences were noted in adverse effects between the two treatment groups. Interpretation EGCG and cognitive training for 12 months was significantly more effective than placebo and cognitive training at improving visual recognition memory, inhibitory control, and adaptive behaviour. Phase 3 trials with a larger population of individuals with Down's syndrome will be needed to assess and confirm the long-term efficacy of EGCG and cognitive training.

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