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Project 3 - Novel Biomarkers in Alexander Disease

Alexander Disease (AxD) is a neurodegenerative disorder caused by the accumulation of an intermediate filament protein known as Glial Fibrillary Acidic Protein (GFAP) in astrocytes. Exciting novel studies in murine models have demonstrated the ability to decrease aberrant GFAP using antisense oligonucleotide (ASO) technology. These advances offer tremendous hope for this devastating disease, leading families, advocacy groups, clinicians, and researchers to seek prompt initiation of clinical trials.

However, translating these findings into effective treatments is limited by the lack of data qualifying GFAP as a responsive biomarker for such a clinical trial. Project 3, therefore, aims to address the internal validity of multicenter GFAP testing methodologies, including intra-assay and inter-assay precision and accuracy, and advance our understanding of variability in GFAP levels by clinical disease subtypes. This project also seeks to examine the relationships between clinical subtypes, GFAP levels, and clinical outcome assessments.


The first aim seeks to obtain longitudinal GFAP measurements in CSF and plasma samples of 40 Alexander Disease patients across multiple sites. Investigators will test sample stability over various shipping and storing conditions and assay reliability through intra- and inter-assay measurements.

This aim seeks to determine whether GFAP concentrations vary by clinical subtypes of Alexander's Disease. The disorder presents at various ages, with different clinical phenotypes, and investigators hope to determine whether these features accurately predict GFAP elevations.

The final aim will further explore whether GFAP levels predict functional outcome measures in Alexander Disease. To address this question, investigators will leverage the longitudinal motor, cognitive, and swallowing tools defined as part of Project 1.

The expected outcome of these aims is a more comprehensive understanding of GFAP levels in Alexander's Disease. These investigations will provide a critical foundation of knowledge on which to base the design of future clinical trials.