Migraine Medication Olcegepant Shows Promise In Reducing COVID-19 Symptoms In Older Mice
Nikhil Prasad Fact checked by:Thailand Medical New Team Jun 01, 2024 5 months, 3 weeks, 1 day, 23 hours, 16 minutes ago
COVID-19 News: Scientists at the University of Rochester Medical Center and Cornell University have discovered a promising new application for a migraine medication, olcegepant. Known for its effectiveness in treating migraines, olcegepant may also mitigate some of the more debilitating symptoms of COVID-19. This study covered in this
COVID-19 News report, highlights olcegepant's potential to reduce weight loss and the release of interleukin 6 (IL-6), a key marker of inflammation, in older mice infected with a mouse-adapted version of SARS-CoV-2.
Migraine Medication Olcegepant Shows Promise In Reducing COVID-19 Symptoms In Older Mice
Bronchoalveolar lavage (BAL) samples were obtained for ELISA testing, and lungs were obtained for subsequent immunohistochemistry at 3 dpi and were analyzed with nested 1-way ANOVA. MA10-SARS-CoV-2 infection increased the release of the inflammatory cytokine IL-6, and this IL-6 release was attenuated by the CGRP signaling blockade. In both C57BL/6J (A) and 129S (B) mouse strains, IL-6 release was attenuated by olcegepant SQ release. Moreover, in αCGRP-null mice (αCGRP-KO), IL-6 cytokine release was statistically equivalent to infected controls given olcegepant and uninfected controls.
The Neurological Impact of COVID-19
COVID-19 has been associated with various neurological symptoms such as fever, dizziness, and nausea. However, the neurological aspects of SARS-CoV-2 infection have been scarcely studied in animal models. Researchers aimed to fill this gap by using two common wild-type mouse lines (C57BL/6J and 129/SvEv) and a 129S calcitonin gene-related peptide (αCGRP) null-line. These mice were infected with a mouse-adapted version of SARS-CoV-2 to simulate COVID-19 infection and study its neurological impact.
Introducing Olcegepant: A Migraine Drug with Potential New Uses
Olcegepant is a CGRP receptor antagonist, traditionally used to treat migraines. Researchers hypothesized that it might also mitigate the neuroinflammatory and neurological signs associated with SARS-CoV-2 infection. They conducted experiments to evaluate if blocking CGRP signaling with olcegepant could protect older mice from permanent weight loss and reduce acute neuroinflammatory responses.
Weight Loss and Neurological Symptoms
Older mice infected with the virus showed acute symptoms such as fever, dizziness, and nausea. However, those treated with olcegepant displayed significantly less weight loss compared to untreated mice. This suggests that olcegepant could help alleviate some of the more severe physical symptoms associated with COVID-19 in older individuals.
IL-6: A Marker of Inflammation
One of the critical findings of the study was the effect of olcegepant on IL-6 levels. IL-6 is an inflammatory cytokine often elevated in COVID-19 patients, contributing to the infamous "cytokine storm." Researc
hers found that olcegepant significantly reduced IL-6 levels in both wild-type mouse lines. In mice lacking αCGRP, IL-6 release was almost negligible. This indicates that CGRP receptor signaling is closely linked to IL-6 production, suggesting that migraine inhibitors could play a role in controlling COVID-19-related inflammation.
Nausea and Dizziness: Common Yet Overlooked Symptoms
Nausea and dizziness are early and common neurological symptoms of COVID-19. Studies have shown that around 30% of COVID-19 patients experience dizziness, and 26% suffer from nausea. These symptoms, though often labeled as gastrointestinal problems, may actually stem from the autonomic nervous system's response to the virus.
The Role of CGRP in COVID-19
CGRP is a neuropeptide involved in the body's response to pain and inflammation. It has been implicated in the neurological symptoms of COVID-19, such as fever, headache, dizziness, and nausea. The study found that SARS-CoV-2 activates transient receptor potential (TRP) channels, leading to CGRP release and subsequent IL-6 production. This interplay between CGRP and IL-6 might explain the severe inflammatory and neurological symptoms observed in COVID-19 patients.
Exploring the Mechanisms
To further understand this relationship, researchers used a mouse model to assess nausea and dizziness induced by SARS-CoV-2 infection. They measured temperature changes in mice subjected to provocative motion, a method previously used to study migraine-induced nausea. The results showed that infection caused a delay in temperature recovery, indicative of a nausea-like state. Interestingly, olcegepant treatment did not show protective effects on these acute nausea responses but significantly reduced weight loss and IL-6 levels.
Broader Implications for Treatment
This study's findings suggest that migraine medications targeting CGRP signaling could be repurposed to treat COVID-19 symptoms, particularly in older patients. Given that older individuals are more susceptible to severe COVID-19 and higher mortality rates, this could have significant therapeutic implications. Moreover, the reduced IL-6 levels in treated mice indicate that olcegepant and similar drugs might help manage the inflammatory response in COVID-19, potentially preventing the progression to severe disease.
Future Directions
The promising results from this study pave the way for further research into the use of CGRP antagonists in treating COVID-19. Future studies could explore different dosages and treatment regimens, investigate the long-term effects of such treatments, and assess their efficacy in other coronaviral infections. Additionally, the potential for these drugs to mitigate long COVID symptoms, which also involve elevated IL-6 levels, warrants further investigation.
Conclusion
In summary, this groundbreaking study reveals that olcegepant, a migraine medication, has the potential to alleviate some of the severe symptoms of COVID-19 in older mice. By reducing weight loss and IL-6 levels, olcegepant could help manage the neuroinflammatory responses associated with the virus. These findings open new avenues for repurposing existing drugs to combat COVID-19 and related viral infections, highlighting the importance of continued research in this field.
The study findings were published in the peer reviewed Journal of Virology.
https://journals.asm.org/doi/10.1128/jvi.00066-24
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