Author: Leanne Winner
Winner, Leanne, 2024 Identification and early validation of blood-based biomarkers of central nervous system disease in Sanfilippo syndrome, a childhood dementia, Flinders University, College of Medicine and Public Health
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Sanfilippo syndrome causes childhood dementia in 1/66,000 live births. These infants are born apparently healthy with symptoms occurring from ~2 years of age. There are no approved treatments, but clinical trials indicate pre-symptomatic treatment is essential to maintain healthy development. Regulatory approval of treatment is currently hindered by the absence of laboratory-based biomarkers able to quantify the resolution of relevant neuropathology. Using a murine model of Sanfilippo type A, we reveal the aberrant expression of novel proteins involved in the neurodegenerative process in cerebral cortex that warrant consideration for biomarker development. Our murine and Sanfilippo patient blood data highlight that glial fibrillary acidic protein and neurofilament light are clinically relevant blood-based biomarkers of neurodegenerative disease, with immediate clinical potential. Furthermore, in Sanfilippo mice we demonstrate that pre-symptomatic gene therapy prevents the elevation of these proteins, supporting their future use as neuropathologically relevant response-to-treatment blood-based biomarkers in Sanfilippo patients.
Keywords: Sanfilippo, mucopolysaccharidosis, childhood dementia, biomarkers, MPS
Subject: Medical Science thesis
Thesis type: Doctor of Philosophy
Completed: 2024
School: College of Medicine and Public Health
Supervisor: Prof. Kim Hemsley