2021 MSUFCU Grand Prize Award for the Lyman Briggs Research Showcase
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FDA Approved Drug Bicalutamide Rescues Male Mice from Kennedy’s Disease Mackenzie Greene, 3rd year |
Abstract
Kennedy’s Disease (KD) is a neurodegenerative disorder caused by a polyglutamine expansion, or CAG repeat, in the Androgen Receptor (AR) gene. This disease affects only males, usually emerges mid-life, and is characterized by marked deficits in muscle strength and coordination. Male mice with the KD allele develop muscle weakness around puberty as testosterone levels surge, suggesting that levels of testosterone may contribute to disease development in mice with mutated AR.
Bicalutamide (Casodex Brand) is a drug currently being prescribed to slow progression of prostate cancer. By binding to androgen receptors to block androgens like testosterone, bicalutamide prevents the detection and effects of testosterone. We hypothesize that giving bicalutamide to male mice carrying the mutated AR allele will slow or prevent disease progression. We monitored the integrity of their motor function over time based on measures of hang time, grip strength, and ambulatory function in an open field. When one mouse in the trial reached a certain disease threshold indicated by weakness, all animals in the trial were sacrificed and muscle size and body weight were analyzed. Disease symptoms were significantly less for mice who received bicalutamide compared to the vehicle-treated mice, demonstrating a clear benefit of this drug in a mouse model of KD. Bicalutamide is currently approved for use as a treatment for prostate cancer, and our findings suggest that this drug may be an effective therapeutic for patients afflicted by KD.