methylation, acetylation, and SUMOylation. The polyglutamine androgen receptor has been found to have different levels of some these post-translational modifications. Further, altering the levels of certain post-translational modifications of the mutant androgen receptor has altered the degree of toxicity in cellular and animal models, suggesting they may be a target for further research and therapeutic development. Clinical trials Leuprorelin Leuprorelin, a GnRH agonist which blocks the synthesis of testosterone when given continuously, was initially shown to be effective at improving motor function in mouse models of SBMA. A small pilot study was performed in which five SBMA patients were given subcutaneous injections of leuprorelin every four weeks for six months, with serial scrotal skin biopsies performed. Nuclear accumulation of polyglutamine androgen receptor was significantly reduced in patient scrotal biopsies. Additionally, serum CK, a marker of muscle deterioration, and testosterone levels were both reduced in patients receiving leuprorelin. Notably, in this study patients were not randomized to treatment groups or placebo controlled. A subsequent larger study consisted of fifty SBMA patients randomized to either leuprorelin treatment or placebo. This trial spanned 48 weeks of treatment with treatment occurring every four weeks initially. Following treatment, thirty-four patients had an open-label follow-up spanning an additional ninety-six weeks with treatment continuing every twelve weeks. At the forty-eight week mark, there was no significant difference in the ALS functional rating scale, the primary outcome measure of the study, between placebo and leuprorelin treated groups. There was improvement in swallowing a barium contrast marker, a secondary endpoint of the study, at forty-eight weeks. Further, there was improvement in the ALS functional rating scale at the 96 and 144 week marks, suggesting a longer period may be needed to see effects of leuprorelin. A larger, multi-center, placebo-controlled, double blind study was then conducted which contained 199 SBMA patients who were randomized to either placebo or leuprorelin treatment. The study spanned forty-eight weeks with leuprorelin treatment every 12 weeks, with ability to swallow a barium contrast marker as the primary endpoint. In this study, there was not a significant difference in barium swallow at forty-eight weeks. There was also no difference in other video fluorography measurements, supporting the lack of improvement in swallow function in the treatment group. Other secondary measures, such as number of AR positive scrotal cells and serum CK level were significantly different in the treatment group. Though the primary endpoint of the study did