Affiliations: [a] Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
| [b]
Howard Hughes Medical Institute, Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN, USA
| [c]
Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
| [d]
Department of Rehabilitation Medicine, Clinical Center, Department of Health and Human Services, NIH, Bethesda, MD, USA
Correspondence:
[*]
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.grunseich@nih.gov.
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
