title: Sexual Reassignment Fails to Prevent Kennedy's Disease.
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.
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Lanman
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Dara
authors.initials: D
authors.lastname: Bakar
authors.affiliation: Howard Hughes Medical Institute, Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Nisha M
authors.initials: NM
authors.lastname: Badders
authors.affiliation: Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Ailbhe
authors.initials: A
authors.lastname: Burke
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Kokkinis
authors.affiliation: Department of Rehabilitation Medicine, Clinical Center, Department of Health and Human Services, NIH, Bethesda, MD, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Shrader
authors.affiliation: Department of Rehabilitation Medicine, Clinical Center, Department of Health and Human Services, NIH, Bethesda, MD, USA.
authors.forename: Galen O
authors.initials: GO
authors.lastname: Joe
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Schindler
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Bott
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: George G
authors.initials: GG
authors.lastname: Harmison
authors.affiliation: Howard Hughes Medical Institute, Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Taylor
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Fischbeck
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Grunseich
mesh_terms: D000726:Androgen Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D055534:Bulbo-Spinal Atrophy, X-Linked / Q000517:prevention & control*; D004195:Disease Models, Animal; D004330:Drosophila; D005260:Female; D006801:Humans; D008297:Male; D051381:Rats; D057829:Gender-Affirming Procedures / Q000379:methods*; D013148:Spironolactone / Q000009:adverse effects / Q000494:pharmacology*; D014189:Transsexualism / Q000628:therapy*
chemical_list: D000726:Androgen Antagonists; D013148:Spironolactone
keywords: Motor neuron disease; X-Linked; androgen; bulbo-spinal atrophy; receptors; spironolactone