Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target – an fMRI study

Autor: Hauke Basedau, Lisa-Marie Sturm, Jan Mehnert, Kuan-Po Peng, Marlene Schellong, Arne May
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: eLife, Vol 11 (2022)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.77146
Popis: Background: 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. Methods: 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. Results: 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. Conclusions: 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. Funding: 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. Clinical trial number: The basic science study was preregistered in the Open Science Framework (https://osf.io/m2rc6).
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