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

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Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target - an fMRI study. / Basedau, Hauke; Sturm, Lisa-Marie; Mehnert, Jan; Peng, Kuan-Po; Schellong, Marlene; May, Arne.

In: ELIFE, Vol. 11, e77146, 23.05.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Basedau, H, Sturm, L-M, Mehnert, J, Peng, K-P, Schellong, M & May, A 2022, 'Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target - an fMRI study', ELIFE, vol. 11, e77146. https://doi.org/10.7554/eLife.77146

APA

Basedau, H., Sturm, L-M., Mehnert, J., Peng, K-P., Schellong, M., & May, A. (2022). Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target - an fMRI study. ELIFE, 11, [e77146]. https://doi.org/10.7554/eLife.77146

Vancouver

Basedau H, Sturm L-M, Mehnert J, Peng K-P, Schellong M, May A. Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target - an fMRI study. ELIFE. 2022 May 23;11. e77146. https://doi.org/10.7554/eLife.77146

Bibtex

@article{36a42d042d4d430a8fa4061bf9bf72a7,
title = "Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target - an fMRI study",
abstract = "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).",
author = "Hauke Basedau and Lisa-Marie Sturm and Jan Mehnert and Kuan-Po Peng and Marlene Schellong and Arne May",
note = "{\textcopyright} 2022, Basedau et al.",
year = "2022",
month = may,
day = "23",
doi = "10.7554/eLife.77146",
language = "English",
volume = "11",
journal = "ELIFE",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS

TY - JOUR

T1 - Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target - an fMRI study

AU - Basedau, Hauke

AU - Sturm, Lisa-Marie

AU - Mehnert, Jan

AU - Peng, Kuan-Po

AU - Schellong, Marlene

AU - May, Arne

N1 - © 2022, Basedau et al.

PY - 2022/5/23

Y1 - 2022/5/23

N2 - 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).

AB - 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).

U2 - 10.7554/eLife.77146

DO - 10.7554/eLife.77146

M3 - SCORING: Journal article

C2 - 35604755

VL - 11

JO - ELIFE

JF - ELIFE

SN - 2050-084X

M1 - e77146

ER -