Is repurposing of CGRP antagonists for asthma a strategy worth pursuing?

Nicolaas, Patrice (2025) Is repurposing of CGRP antagonists for asthma a strategy worth pursuing? Bachelor's Research Project, Pharmacy.

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Abstract

Asthma is a disease that affects 262 million people worldwide. The symptoms result from an inflammatory reaction to irritants that would not provoke the same response in healthy individuals. Severe cases of asthma are often characterized by airway remodeling, which includes an increase in sensory neurons. These neurons produce CGRP, which is also elevated in fatal asthma. Some severe cases of asthma are unresponsive to current treatments, and CGRP antagonists may represent a potential new treatment option. We utilized cell databases, mast cell gene expression studies, and a literature review to investigate this possibility. The primary source of CGRP in asthma was identified as pulmonary endocrine cells, which are also elevated in asthma. Most CGRP receptors were found on the endothelial cells of blood vessels, aligning with the mechanism of CGRP antagonists in migraines, where they inhibit vasodilation. CGRP is thought to increase mast cell activity, though this has not yet been confirmed by laboratory results, as qRT-PCR analysis showed no significant difference after CGRP stimulation of mast cells. The literature review concluded that CGRP’s anti-inflammatory effects mainly occur through eosinophils, mast cells, ILC2 cells, and Th2 cells. Additionally, CGRP exerts tissue-protective effects by increasing IL-10, promoting regulatory T-cells, and inhibiting dendritic cell migration. In conclusion, repurposing CGRP antagonists appears to be a promising strategy, given their effect on eosinophils and mast cells, two key players in asthma pathology and possible vasodilatory effects.

Item Type:	Thesis (Bachelor's Research Project)
Supervisor name:	Gosens, R.
Degree programme:	Pharmacy
Thesis type:	Bachelor's Research Project
Language:	English
Date Deposited:	07 Apr 2025 14:44
Last Modified:	07 Apr 2025 14:44
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/34971

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