Affiliations: [a] Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
Howard Hughes Medical Institute, Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN, USA
Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Department of Rehabilitation Medicine, Clinical Center, Department of Health and Human Services, NIH, Bethesda, MD, USA
Correspondence to: Dr. Grunseich, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, 2A-1000 Building 35, 35 Convent Drive, NIH, Bethesda, MD 20892, USA. Tel.: +1 301 402 5423; E-mail: christopher.[email protected].
Abstract: 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.
Keywords: Motor neuron disease, bulbo-spinal atrophy, X-Linked, spironolactone, receptors, androgen