From mouse to human – Establishing novel biomarkers for APBD
Awardee: Felix Nitschke
Institution: University of Texas Southwestern Medical Center
Grant Amount: $56,857
Funding Period: February 1, 2025 - January 31, 2026
Summary:
APBD is caused by recessive mutations in the glycogen branching enzyme gene (GBE1), and the consequent accumulation of poorly branched cytosolic glycogen aggregates called polyglucosan bodies (PBs) in the nervous system. There are several treatment options in different stages of preclinical development. There is a critical need for robust disease biomarkers to determine disease progression and treatment efficacy in any future clinical trial in the US. We propose to evaluate a novel glycogen-related metabolite as biomarker candidates in an integrated approach using non-invasive imaging techniques and body fluid analyses from both the APBD mouse model and patients. We will deliver systematic proof of concept and quantify glycoNOE MRI signal in APBD mice and controls. Second, we will correlate the glycoNOE signal to biochemical quantification of MOG, soluble and insoluble glycogen, as well as neuroinflammatory markers including blood and CSF NfL and GFAP. Additionally, we will probe the biomarker potential of glycoNOE MRI, NfL and GFAP in blood and CSF of a small APBD patient cohort. APBD patients will be recruited for research visit to UTSW for glycoNOE MRI brain scanning and collection of CSF, blood and urine (through UTSW biobank). High fidelity assays will be used to measure NfL and GFAP for correlation to disease state.