Announcing the 2025 End AxD Grant Program Recipients
End AxD is proud to announce the recipients of the inaugural 2025 End AxD Grant Program. Following a review of 24 applications from around the world, the End AxD Scientific Advisory Committee has recommended five pioneering research projects for funding.
This year’s program represents an initial 2025 commitment of $263,419 with potential for year two investment of $266,928, pending mid-term progress reports.
End AxD’s investment strategy this year focuses not only on advancing the therapeutic pipeline but also on deepening our understanding of fundamental disease mechanisms and building high-value, long-term tools, such as specialized antibodies and protein ligands, that will empower the wider research community to accelerate discoveries that will lead to potential treatments.
Albee Messing, VMD, PhD, Chair of the End AxD Scientific Advisory Committee concluded: "We were impressed by the uniformly high quality of the research proposals that were submitted and only wish that we could have funded more. Alexander disease is a very rare disease. But its root cause involves one of the brain’s most abundant proteins, GFAP, and one of its most abundant cell types, the astrocyte. We imagine that understanding how changes in this protein and cell lead to catastrophic changes throughout the central nervous system will provide a unique window into the role that astrocyte dysfunction plays in the much more common neurodegenerative disorders such as Alzheimer’s and Parkinson’s.”
"On behalf of the End AxD Board, I want to express our deepest gratitude to the scientific community and our dedicated donors who make this work possible. Seeing the caliber and creativity of these projects gives us immense hope. We are not just funding research; we are building a multi-front offensive against this disease. Each of these investigators brings a unique expertise that moves us closer to a future where Alexander Disease is no longer a life-limiting diagnosis. As Dr Messing said, we only wish that we could have funded more", Thomas Wagner, Research Advocacy Lead, End AxD Board of Directors.
2025 Grant Award Highlights (in alphabetical order)
1. Identification of first-in-class ligands that bind glial fibrillary acidic protein (GFAP)
Dr. Alison Axtman (UNC Chapel Hill) and Co-Investigator Dr. Levon Halabelian (Structural Genomics Consortium, University of Toronto) are working to turn GFAP into a "druggable" target. By identifying the first small molecules that bind directly to the GFAP protein, they are creating essential tool compounds that the entire scientific community can use to manipulate and study GFAP in unprecedented ways, and set the foundation for potential small molecule drugs targeting GFAP.
“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”. - Dr Alison Axtman and Dr Levon Halabelian
2. Targeting Mutant GFAP Driven AxD Astrocyte Pathology
Dr. Benjamin L.L. Clayton (Case Western Reserve University) is pursuing a dual strategy to address astrocyte dysfunction. His team will utilize high-throughput chemical screening of 10,000 bioactive drugs to identify compounds that suppress GFAP pathology. Simultaneously, the project will rigorously map the transcriptional and epigenetic landscape of AxD astrocytes, providing a foundational molecular "atlas" of how mutant GFAP alters cellular identity.
“We are deeply grateful for this generous support from End AxD that will allow us to fill critical gaps in the understanding of Alexander Disease and will support our search for drugs that we hope will bring urgently needed treatments to patients.” - Dr Benjamin L.L. Clayton
3. Evaluating the therapeutic potential of Gfap disruptive Cas9 nuclease delivered by lipid nanoparticles in a murine model of Alexander disease
Dr. Vasco Meneghini (San Raffaele Telethon Institute for Gene Therapy) is exploring a non-viral delivery method for CRISPR-Cas9 gene editing. By using lipid nanoparticles (LNPs) rather than traditional viral vectors, this project seeks to develop a safer, single-dose strategy to silence the mutant GFAP gene while minimizing potential immunogenicity.
“The support of the End AxD program is essential to advance the translational research in this fatal rare disease. As an early-career scientist, receiving an End AxD grant represents a crucial opportunity to expand the network of experts and clinicians, further develop innovative research, and accelerate the translation of scientific discoveries into meaningful therapeutic strategies for patients.” - Dr Vasco Meneghini
4. Development of Novel Monoclonal Anti-GFAP Antibodies for Precise Detection of GFAP Proteoforms in Alexander Disease:
Dr. Ming-Der Perng (National Tsing Hua University) is addressing a critical tool-gap in the field. His team is developing monoclonal antibodies capable of distinguishing normal GFAP from the abnormal forms found in Rosenthal fibers. These tools will be shared with the broader research community to improve diagnostic precision and track disease progression in both laboratory and clinical settings.
5. What causes myelin loss in Alexander disease?
Dr. J. Bradley Zuchero (Stanford University) is investigating the "unified framework" of myelin loss. His research examines a specific signaling pathway between astrocytes and oligodendrocytes that may trigger the degradation of white matter. Understanding this basic mechanism could unlock therapeutic strategies to preserve myelin, potentially bridging insights between AxD and other demyelinating conditions.
You can download the announcement with an overview of all projects here.
