Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Elife. 2022 May 23;11:e77146. doi: 10.7554/eLife.77146.
Monoclonal antibodies (mAbs) against calcitonin gene-related peptides (CGRP) are novel treatments for migraine prevention. Based on a previous functional imaging study which investigated the CGRP receptor mAb (erenumab), we hypothesized that (i) the CGRP ligand mAb galcanezumab would alter central trigeminal pain processing; (ii) responders to galcanezumab treatment would show specific hypothalamic modulation in contrast to non-responders; and (iii) the ligand and the receptor antibody differ in brain responses.
Using an established trigeminal nociceptive functional magnetic imaging paradigm, 26 migraine patients were subsequently scanned twice: before and 2-3 weeks after administration of galcanezumab.
We found that galcanezumab decreases hypothalamic activation in all patients and that the reduction was stronger in responders than in non-responders. Contrasting erenumab and galcanezumab showed that both antibodies activate a distinct network. We also found that pre-treatment activity of the spinal trigeminal nucleus (STN) and coupling between the STN and the hypothalamus covariates with the response to galcanezumab.
These data suggest that despite relative impermeability of the blood-brain barrier for CGRP mAb, mAb treatment induces certain and highly specific brain effects which may be part of the mechanism of their efficacy in migraine treatment.
This work was supported by the German Ministry of Education and Research (BMBF) of ERA-Net Neuron under the project code BIOMIGA (01EW2002 to AM) and by the German Research Foundation (SFB936-178316478-A5 to AM). The funding sources did not influence study conduction in any way.
The basic science study was preregistered in the Open Science Framework (https://osf.io/m2rc6).
针对降钙素基因相关肽（CGRP）的单克隆抗体（mAbs）是偏头痛预防的新疗法。基于一项先前针对 CGRP 受体 mAb（erenumab）的功能影像学研究，我们假设：（i）CGRP 配体 mAb galcanezumab 将改变中枢三叉神经疼痛处理；（ii）galcanezumab 治疗的应答者与非应答者相比会显示特定的下丘脑调制；（iii）配体和受体抗体在大脑反应中存在差异。
使用已建立的三叉神经伤害性功能性磁共振成像范式，26 名偏头痛患者随后接受了两次扫描：在给予 galcanezumab 之前和 2-3 周后。
我们发现 galcanezumab 降低了所有患者的下丘脑激活，并且在应答者中比在非应答者中降低得更强。对比 erenumab 和 galcanezumab 显示，两种抗体激活了不同的网络。我们还发现，脊髓三叉神经核（STN）的预处理活性和 STN 与下丘脑之间的耦合与 galcanezumab 的反应相关。
这些数据表明，尽管 CGRP mAb 对血脑屏障相对不可渗透，但 mAb 治疗会诱导出某些高度特异的大脑效应，这些效应可能是其在偏头痛治疗中的疗效机制的一部分。
这项工作得到了德国教育和研究部（BMBF）在神经科学 ERA-Net 项目下的支持（BIOMIGA，项目编号 01EW2002，授予 AM），以及德国研究基金会（SFB936-178316478-A5，授予 AM）。资金来源在任何方面都没有影响研究的进行。
基础科学研究已在开放科学框架（https://osf.io/m2rc6）中预先注册。
