Growth hormone rescue cerebellar degeneration in SCA3 transgenic mice

Spinocerebellar ataxia type 3 (SCA3) is a fatal neurodegenerative disease for which no identified effective treatment or prevention methods exist. However, low-dose growth hormone (GH) therapy, as a potential off-label use, may deter the progress of SCA3. SCA3 15Q and SCA3 84Q transgenic mice harboring a YAC transgene that expresses the human ATXN3 gene with a pathogenic expanded 15 CAG repeat and 84 CAG repeat motif, respectively, were recruited. SCA3 15Q transgenic mice were considered as the healthy control group, whereas low-dose GH- and PBS-treated SCA3 84Q transgenic mice were considered as the study and sham groups, respectively. The SCA3 84Q transgenic mice were administered intraperitoneal injections of GH or PBS weekly from the postnatal age of 9 months-18 months. After 9 months of GH treatment in the SCA3 84Q transgenic mice, all locomotor functions including rotarod test, behavior box analysis were restored. The GH-treated SCA3 84Q transgenic mice revealed more preserved Purkinje cells/cerebellar cortex and less ataxin-3 aggregation, DNA oxidative, cell apoptosis compared with the PBS-treated SCA3 84Q transgenic mice. GH therapy may be one of the potential off-labeled using in the alleviation of SCA3 progression.