were found to increase during intense exercise, indicating primary myopathy. In a study of home-based functional exercise with 50 SBMA patients, both the low-intensity exercise and stretching control groups tolerated exercise well, but there was no significant difference in primary and secondary outcomes between the two groups. However, subgroup analysis did show benefit for a low-functioning group, suggesting there may be a role for exercise in these patients. In a third study, high-intensity interval training (HIIT) for less than one hour per week, improved both VO2max and performed workload, without increasing CK levels, self-rated fatigue and pain. Overall, these results suggest that exercise programs should be individually tailored, and SBMA patients must be carefully monitored for maladaptive biomarkers (increasing CK levels) to prevent muscle damage and worsening of disease phenotypes. History SBMA was first described in Japanese literature in 1897 by Hiroshi Kawahara in a case report detailing progressive bulbar palsy in two brothers. Information on the clinical course, X-linked inheritance patterns, and key pathologic features was later documented by William R. Kennedy in 1968. Onset of disease in mid-life and lack of symptoms in heterozygous female carriers was further described by Anita Harding in 1982. In 1986, the causative gene of SBMA was shown to be present on the proximal arm of the X chromosome by Kurt Fischbeck, though the exact gene causing SBMA had not yet been characterized. In 1991, it was discovered that the AR gene is involved in the disease process, and that expansion of a CAG repeat in the AR gene causes disease. Research directions Research in SBMA is broad, and covers a number of aspects of the disorder. Below is a summary of a few areas of ongoing research in SBMA: Aggregation The polyglutamine androgen receptor does not fold properly, and subsequently forms protein aggregates with other proteins. This is a gain of new function conferred by the polyglutamine tract, as the non-polyglutamine expanded androgen receptor does not form these aggregates. Several proteins key to normal cellular function have been found to be sequestered within these aggregates, including CREB-BP, Hsp70, Hsp40, and components of the ubiquitin proteasome system. It is thought that loss of sufficient supply of these and other key proteins contributes to the pathogenesis of the disease, though further research is ongoing. Post-translational modifications Following its transcription and translation, the androgen receptor is modified with a number of post-translational modifications, including phosphorylation,