Assessment of Long-Term Safety and Efficacy of Purple Sweet Potato Color (PSPC) and Myo-Inositol (MI) Treatment for Motor Related and Behavioral Phenotypes in a Mouse Model of Classic Galactosemia

Abstract

Classic galactosemia (CG) is a rare inherited metabolic disease caused by mutations in the GALT gene encoding the enzyme galactose-1 phosphate uridylyltransferase in galactose metabolism. The condition develops as a potentially fatal illness during the newborn period, but its acute clinical manifestations can be alleviated through a galactose restricted diet. Nonetheless, such dietary intervention is inadequate in preventing significant long-term consequences, including neurological impairments, growth restriction, cognitive delays, and, for most females, primary ovarian insufficiency. At present, no effective therapy exists to stop the progression of these complications, highlighting the urgent need for new treatment approaches to be developed. Supplements have been used in the treatment of other inborn errors of metabolism; however, they are not typically included in the clinical therapeutic regimen for CG. Recently, our research team has demonstrated that two generally recognized as safe supplements (purple weet potato color, PSPC and myo-inositol, MI) have been effective in partially restoring functions in the ovaries of our GalT-KO mouse model. However, the toxicological profile of both PSPC and MI has not been determined. In this study, we investigated the acute (30 days) and chronic (180 days) oral toxicities of PSPC and MI both in WT control and GalT-KO mice. Furthermore, our study aims to evaluate the effectiveness of oral feeding of PSPC and MI in correcting motor-related and behavioral phenotypes in GalT-KO mice. The long-term treatment of MI at a lower dose demonstrated promising improvements in motor deficit and anxiety driven hyperactivity in the mutant mice.