Migraine Drug Olcegepant Reduces Weight Loss and Inflammation in COVID-Infected Older Mice
Blocking CGRP with the migraine drug olcegepant reduced permanent weight loss and IL-6 inflammation in older mice infected with SARS-CoV-2.
Quick Facts
What This Study Found
Older mice (over 18 months, roughly equivalent to elderly humans) infected with mouse-adapted SARS-CoV-2 showed neurological symptoms including fever, dizziness, and nausea in two wild-type strains (C57BL/6J and 129/SvEv).
Olcegepant treatment protected against the permanent weight loss seen after infection. It also dramatically reduced IL-6 levels in both mouse strains. The most striking finding: CGRP-knockout mice (lacking the alpha-CGRP gene entirely) showed virtually no IL-6 release after infection.
The fever, dizziness, and nausea occurred in all older mice regardless of treatment, suggesting CGRP blockade acts on the inflammatory cascade rather than preventing initial neurological symptoms.
Key Numbers
- Mice over 18 months old (equivalent to elderly humans)
- Two wild-type strains tested: C57BL/6J and 129/SvEv
- CGRP-null mice: virtually no IL-6 release
- Olcegepant: reduced permanent weight loss and IL-6 in both strains
- All older mice developed fever, dizziness, and nausea regardless of treatment
How They Did This
Researchers infected C57BL/6J mice, 129/SvEv mice, and 129S αCGRP-null mice with mouse-adapted SARS-CoV-2. Older mice (over 18 months) were used because age is a major COVID-19 risk factor. They tested olcegepant (CGRP receptor antagonist) for protection against weight loss and measured IL-6 levels and neurological symptoms (fever using thermoregulation, dizziness using postural sway, nausea using behavioral surrogates).
Why This Research Matters
COVID-19 neurological symptoms (headache, dizziness, brain fog) have been a persistent challenge. CGRP is a known neuroinflammatory mediator. This study shows that blocking CGRP can reduce the inflammatory cytokine response to SARS-CoV-2, particularly IL-6 (which was associated with severe COVID-19 outcomes). If confirmed, migraine drugs could be repurposed for COVID-19 neurological complications.
The Bigger Picture
COVID neurological symptoms like headache, dizziness, and brain fog are persistent challenges. CGRP is a known neuroinflammatory mediator, and blocking it could address the inflammatory component of COVID neurological disease.
What This Study Doesn't Tell Us
This was tested in mice with mouse-adapted SARS-CoV-2, not human COVID-19. The mouse strains and viral adaptation may not replicate human disease. Olcegepant is an intravenous CGRP blocker not approved for clinical use (gepant pills like rimegepant are available). The study measured acute IL-6 and weight loss but not long-term neurological outcomes. The behavioral surrogates for human neurological symptoms are approximations.
Questions This Raises
- ?Could gepant drugs help with long COVID neurological symptoms?
- ?Does this CGRP-inflammation link apply to other viral infections?
Trust & Context
- Key Stat:
- CGRP-null mice: no IL-6 Mice genetically lacking CGRP showed virtually no IL-6 inflammatory response to COVID infection
- Evidence Grade:
- Rated preliminary: animal study with mouse-adapted SARS-CoV-2, not human COVID-19. The model and drug may not directly translate.
- Study Age:
- Published in 2024. Relevant to ongoing research into neurological effects of COVID-19 and long COVID.
- Original Title:
- Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.
- Published In:
- Journal of virology, 98(7), e0006624 (2024)
- Authors:
- Rahman, Shafaqat M(4), Buchholz, David W, Imbiakha, Brian, Jager, Mason C, Leach, Justin, Osborn, Raven M, Birmingham, Ann O, Dewhurst, Stephen, Aguilar, Hector C, Luebke, Anne E
- Database ID:
- RPEP-09111
Evidence Hierarchy
Frequently Asked Questions
Could migraine drugs help COVID symptoms?
In mice, blocking CGRP reduced neuroinflammation from COVID infection. Whether this translates to human benefit is unknown.
What is CGRP's role in COVID inflammation?
CGRP appears to amplify the inflammatory response, particularly IL-6 release. Blocking CGRP dramatically reduced this inflammation in animal studies.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-09111APA
Rahman, Shafaqat M; Buchholz, David W; Imbiakha, Brian; Jager, Mason C; Leach, Justin; Osborn, Raven M; Birmingham, Ann O; Dewhurst, Stephen; Aguilar, Hector C; Luebke, Anne E. (2024). Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.. Journal of virology, 98(7), e0006624. https://doi.org/10.1128/jvi.00066-24
MLA
Rahman, Shafaqat M, et al. "Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.." Journal of virology, 2024. https://doi.org/10.1128/jvi.00066-24
RethinkPeptides
RethinkPeptides Research Database. "Migraine inhibitor olcegepant reduces weight loss and IL-6 r..." RPEP-09111. Retrieved from https://rethinkpeptides.com/research/rahman-2024-migraine-inhibitor-olcegepant-reduces
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.