Lanman, T.A., Bakar, D., Badders, N.M., Burke, A., Kokkinis, A., Shrader, J.A., Joe, G.O., Schindler, A.B., Bott, L.C., Harmison, G.G., Taylor, J.P., Fischbeck, K.H., Grunseich, C. (2016). Sexual Reassignment Fails to Prevent Kennedy's Disease.  J. Neuromuscul. Dis. 3(1): 121--125.

FBrf0250869

Research paper

Spinal and bulbar muscular atrophy is caused by polyglutamine expansion in the androgen receptor. As an X-linked disease dependent on androgens, symptoms and findings are only fully manifest in males. Here we describe a 40-year-old male-to-female transgender SBMA patient who developed full disease manifestations despite undetectable levels of androgens. We used cell culture and animal models to show that spironolactone, the anti-androgen she had taken for 15 years, promotes nuclear localization and toxicity of the mutant protein, which may explain the disease manifestations in this patient.

PMC10427994 (PMC) (EuropePMC)