重塑“小脑抑制”:重复经颅磁刺激治疗马查多-约瑟夫病的机制解析与精准医疗展望
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1)杭州师范大学附属医院认知与脑疾病研究中心,杭州 311121;2)杭州师范大学附属医院神经内科,杭州 311121

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浙江省精准精神医学重点实验室开放基金(2025A2)和浙江省自然科学基金(LY23C090002)资助项目。


Reshaping “Cerebellar Inhibition”: Mechanistic Insights and Precision Medicine Perspectives for rTMS in Machado-Joseph Disease
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Affiliation:

1)Centre for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 311121, China;2)Department of Neurology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 311121, China

Fund Project:

This work was supported by grants from the Open Research Fund of the Zhejiang Key Laboratory of Precision Psychiatry (2025A2) and the Natural Science Foundation of Zhejiang Province (LY23C090002).

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    摘要:

    马查多-约瑟夫病(Machado-Joseph disease,又称脊髓小脑共济失调3型,spinocerebellar ataxia type 3,SCA3)是全球最常见的常染色体显性遗传性小脑共济失调类型。SCA3具有进行性致残的特征,目前临床仍缺乏有效的疾病修饰疗法。重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)作为一种极具潜力的非侵入性干预手段备受关注,但其临床应用长期受限于刺激方案不统一及治疗机制不明。近期,Chen等发表在Brain Stimulation上的一项里程碑式研究,通过结合高剂量间歇性theta爆发刺激(intermittent theta-burst stimulation,iTBS)与同步经颅磁刺激(transcranial magnetic stimulation,TMS)-脑电图(electroencephalogram,EEG)技术,有效应对了上述挑战。本文对该研究的主要发现进行了深入评述,重点阐述了小脑-皮层抑制(cerebello-cortical inhibition,CBI)功能的恢复是其关键的治疗机制。此外,本文进一步探讨了该研究的广泛意义,提出未来的转化研究应整合加速iTBS(accelerated iTBS,aiTBS)范式、皮层反应测量(cortical response measurements,CRM)及个体化神经导航技术,从而开启共济失调精准神经调控的新纪元。

    Abstract:

    Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

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韩亚真,周洁,陈宇超,高忠明,车先伟.重塑“小脑抑制”:重复经颅磁刺激治疗马查多-约瑟夫病的机制解析与精准医疗展望[J].生物化学与生物物理进展,2026,53(2):505-510

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  • 收稿日期:2026-01-05
  • 最后修改日期:2026-02-03
  • 录用日期:2026-02-01
  • 在线发布日期: 2026-02-02
  • 出版日期: 2026-02-28
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