# Administrative Supplement to CGRP's effect on hearing and balance in a mouse model of migraine

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $192,500

## Abstract

The purpose of this COVID-19 research supplement is to critically evaluate if a calcitonin gene-related
peptide (CGRP) receptor antagonist can mitigate both neuroinflammatory and hyper-immune responses to
SARS-CoV-2 infection. In December 2019, the coronavirus disease (COVID-19) caused by severe acute
respiratory syndrome CoV-2 (SARS-CoV-2) was identified. There are now over ~5.5 million confirmed cases
worldwide (1.6 million US), and 345,000 deaths (~100,000 US). COVID-19 causes a respiratory illness like the
flu with symptoms such as fever, cough, loss of smell, fatigue, sputum production, shortness of breath, sore
throat, headache, chills, and nausea or vomiting. Approximately 80% of people have mild disease and
recover. However, in those remaining 20%, COVID-19 is severe and there is evidence that progression to the
most serious type of COVID-19 illness is related to a hyper-immune response (ie, cytokine storm). Currently,
there are no effective vaccines or treatments available for COVID-19. In this supplement we will test the ability
of CGRP-receptor antagonists to inhibit the neuroimmune consequences of SARS-CoV-2 infection, using
temperature and nausea as an indicator of SARS-CoV2 infection, as we are doing in our parent grant to
assess migraine nausea pain. A humanized mouse model has been developed for studying SARS-CoV2,
where mice express the human angiotensin-converting enzyme 2 (hACE2), enabling us to model Covid-19 in
the mouse. The FDA has recently approved Biohaven Pharmaceuticals to proceed to a phase 2 clinical trial of
its CGRP-receptor antagonist (vazegepant; currently in phase 3 trials for migraine) to treat patients with severe
COVID-19, suggesting that the neuroinflammatory reaction that is initiated by CGRP in response to SARS-
CoV2 could be a therapeutic target for treating severe Covid-19, and that the non-invasive readouts of
neuroinflammation that we are developing could be used to rapidly identify at risk patients. Our hypothesis is
that mild to severe COVID-19 symptoms will occur in the transgenic hACE2 mouse that has been infected with
SARS-CoV-2, and that a CGRP receptor antagonist will mitigate these symptoms. The specific aims are to
test the following hypotheses that transgenic mice and non-carrier littermates infected with SARS-CoV-2 will
exhibit: aim 1) mild severe symptoms based on viral load, and if these symptoms are less severe when treated
with a CGRP-receptor antagonist; and aim 2) reduced fever and nausea-like pain when treated with a CGRP-
receptor antagonist. Information gained from these studies will provide a direct assessment of whether a
CGRP-receptor antagonist can mitigate both mild and severe symptoms associated with SARS-CoV-2
infection. This proposal also impacts the development of robust preclinical in vivo assays of COVID-19
symptoms, paving the way to develop and test future therapeutics for COVID-19.

## Key facts

- **NIH application ID:** 10173048
- **Project number:** 3R01DC017261-03S1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** ANNE E LUEBKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173048

## Citation

> US National Institutes of Health, RePORTER application 10173048, Administrative Supplement to CGRP's effect on hearing and balance in a mouse model of migraine (3R01DC017261-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10173048. Licensed CC0.

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