FLyGT: Female Lymphatic GPCR Therapeutics for Migraine Treatment

2025

We propose to characterize the roles and functions of meningeal lymphatic vessels in migraine, a common and debilitating neurological condition with high prevalence in women. Our preliminary data demonstrates that calcitonin gene related peptide (CGRP), which is elevated during a migraine attack, is capable of significantly reducing lymphatic drainage of the meninges. We will use the Collaborative Cross Resource to define and genetically map the natural variance of meningeal lymphatics between females and males and screen for genetic loci that modify the female prevalence of migraine pathophysiology. Further, we will use cutting-edge techniques and custom-designed molecular beacons to illuminate the druggable receptor repertoire of female lymphatics, followed by a comprehensive characterization of receptor pharmacology. We propose that anti-CGRP receptor medications, currently approved for migraine therapy, act through modifying glymphatic flow and could potentially be repurposed for targeting brain lymphatic drainage. We will evaluate this hypothesis in a 3-arm clinical study with MRI imaging modalities that we have uniquely developed for healthy volunteers and patients with migraine who are either untreated or on anti-CGRP medication. Collectively our proposal aims to "Take FLyGT" by accelerating the pace of Female Lymphatic GPCR Therapeutics for Migraine Treatment.

None of the above

Performing Research or Evaluation

Health-Related Activities

General Public

None

Not Applicable

N/A