Researchers at the Structural Genomics Consortium (SGC), spanning its UNC Chapel Hill and Toronto sites, have been awarded funding through the inaugural 2025 End AxD Grant Program to develop the first small molecules targeting the GFAP protein in Alexander disease (AxD).

The project is led by Alison Axtman (SGC-UNC) and co-led by Levon Halabelian (SGC-Toronto), bringing together complementary expertise across SGC sites to address a key barrier in the field: the lack of chemical tools to study GFAP.

Mutations in GFAP are the underlying cause of AxD, with more than 160 disease-associated variants reported to date. However, the protein has remained largely inaccessible to small-molecule approaches, limiting both mechanistic understanding and progress toward targeted therapies.

To overcome this, the team will integrate protein production, small-molecule screening, and medicinal chemistry to identify first-in-class ligands that bind GFAP. These compounds will enable direct interrogation of GFAP biology and provide a starting point for future therapeutic development.

“Our goal is to accelerate drug discovery for Alexander disease by identifying first-in-class GFAP ligands and making them openly available to the research community”, comments Dr. Levon Halabelian, Principal Investigator at SGC-Toronto.

The award is part of the inaugural End AxD Grant Program, which selected five projects from 24 international applications. The program supports efforts that both advance therapeutic approaches and generate high-value tools for the research community, including initiatives that deepen understanding of astrocyte biology and its role in neurodegenerative disease.

Through its open science model, SGC will ensure that the resulting data, reagents, and chemical matter are made rapidly and openly available, supporting global efforts to study GFAP biology and accelerate progress toward potential treatments for AxD.

Read full announcement on End AxD website: https://www.endaxd.org/news/openlettertoionis-k2g6a