Dr. Porter and Dr. Davidson

Free Sialic Acid Storage Disease (FSASD) is an ultrarare, inherited metabolic disorder characterized by neurodegeneration and shortened life expectancy. Because there are no treatments for FSASD individuals, high priority has been placed on compound evaluation to mitigate disease burden. One well-documented pathological feature of FSASD is hypomyelination in the central nervous system. Myelination is critical to proper functioning of nerve cells and a reduction in myelination, such as with FSASD, has profound consequences on movement and cognition. Clemastine fumarate is a regulatory approved antihistamine that has also been shown to have pro-myelinating effects in several different conditions, including another lysosomal disorder, Krabbe disease. Due to clemastine fumarate’s impact on myelination, we hypothesize that treatment of an FSASD mouse model with this drug will provide disease amelioration. 

Slc17a5^R39C C57Bl/6J mice will be administered clemastine fumarate starting at 7 days of age, a few days prior to initiation of myelination in the central nervous system of mice. Slc17a5^R39C C57Bl/6J mice injected with clemastine fumarate or vehicle, along with littermate controls, will be evaluated for changes in motor function, cognition, and survival. Biomarker and neuropathology assessments will substantiate phenotypic findings. Amelioration of hypomyelination in FSASD mice following clemastine fumarate treatment will highlight an aspect of disease pathology amenable to intervention and pave the way for evaluation of other pro-myelinating compounds. Importantly, benefits observed in an FSASD mouse model will support a Bench to Bedside grant should additional preclinical data be necessary, with the ultimate goal of initiating a clinical trial in FSASD individuals.

Award: $90,059

‍Length of project: 1 year