Science:唐氏综合征认知功能障碍,可以治疗了!

2022-09-04 MedSci原创 MedSci原创

唐氏综合症,也称为 21 三体综合征,影响约 800 名新生儿中的一名,并导致各种临床表现,包括认知能力下降。随着年龄的增长,77% 的患有这种疾病的人会出现与阿尔茨海默病相似的症状。嗅觉能力的逐渐丧

唐氏综合症,也称为 21 三体综合征,每800 名新生儿中可能就有1人,并导致各种临床表现,包括认知能力下降。随着年龄的增长,77% 的患有这种疾病的人会出现与阿尔茨海默病相似的症状。嗅觉能力的逐渐丧失是神经退行性疾病的典型特征,在青春期前也很常见,男性可能会出现性成熟缺陷。

里尔神经科学与认知实验室(Inserm/Université de Lille,里尔大学医院)的 Inserm 团队与洛桑大学医院 (CHUV) 的同行联手测试 GnRH 注射疗法的功效,以改善患者的认知功能一小群唐氏综合症患者。首先,科学家们揭示了唐氏综合症动物模型中 GnRH 神经元的功能障碍及其对与该病症相关的认知功能障碍的影响。然后在七名患者中进行了一项试验性研究,测试 GnRH 脉冲注射疗法。结果很有希望:该疗法改善了认知功能和大脑连接。这项研究已发表在最新一期Science(《科学》)杂志上。

最近的发现表明,表达促性腺激素释放激素 (GnRH) 的神经元——它以通过下丘脑调节生殖而闻名——也可以作用于其他大脑区域,并在其他功能中发挥潜在作用,例如认知。

考虑到这个想法,由 Inserm 研究主任 Vincent Prévot 领导的里尔神经科学与认知实验室团队研究了在唐氏综合症小鼠模型中调节 GnRH 的机制。GnRH是一种通常与生育、生殖相关的激素,但是也可以作用于其他脑区,并影响包括认知在内的其他功能。

实验室证明,在 21 号染色体上发现五类 microRNA 可以调节GnRH激素产生,由于21条染色体增加,这种多余的染色体会导致分泌 GnRH 的神经元出现异常。这些发现在基因和细胞水平上都得到了证实。 Inserm 的科学家们能够证明,在小鼠中观察到的进行性认知和嗅觉缺陷与 GnRH 分泌功能失调密切相关。

恢复 GnRH 产生以恢复认知功能

Inserm 科学家随后能够证明恢复生理 GnRH 系统功能可以恢复三体小鼠的认知和嗅觉功能。

随后,研究者尝试了一种GnRH脉冲疗法来改善唐氏综合征小鼠的症状,这种疗法本身适用于治疗先天性GnRH缺乏症,而通过脉冲可以恢复正常的激素分泌节律。小鼠中,与对照组相比,定期接受脉冲治疗的小鼠嗅觉和认知功能在15天后就能得到一定的恢复。

此外,研究还招募了数名唐氏综合征的患者参与临床试验,7名男性志愿者会接受定时的GnRH皮下注射,持续6个月。治疗前后,研究者分别对他们进行了认知能力和嗅觉测试。

根据临床分析结果,治疗之后,7名患者中有6名的认知功能得到了提升,他们能更好地理解指令,完成推理并拥有更好的注意力和情景记忆能力。不过患者的嗅觉基本没有什么变化。

脉冲GnHR疗法可以在6个月内恢复唐氏综合征患者大脑的功能性连接

大脑成像结果显示,这些患者大脑的功能性连接显著增加了,这也表明治疗增强了大脑皮层某些区域之间的交流,从而改善了认知能力。

研究团队计划进一步开展一项包括女性在内的大规模临床研究,确认新治疗方式的综合疗效。

这项研究虽然不能治愈唐氏综合征,但是通过调控GnHR,部分恢复患者的认知功能障碍,尤其是生命早期使用,有助于认知功能障碍恢复,将可能部分恢复患者的未来的自主生活的功能,这是具有重大的意义的。

参考资料:

[1] A therapy found to improve cognitive function in patients with Down syndrome. Retrieved September 1, 2022 from https://www.eurekalert.org/news-releases/962864?

[2] GnRH replacement rescues cognition in Down Syndrome. Science (2022). DOI: https://doi.org/10.1126/science.abq4515

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    2023-04-05 侠胆医心 来自上海
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    2022-09-05 柳叶一刀
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