title: [Anti-androgen therapy for spinal and bulbar muscular atrophy (SBMA)].
abstract: Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, is an adult-onset lower motor neuron disease caused by the expansion of a trinucleotide CAG repeat encoding a polyglutamine tract within the first exon of the androgen receptor (AR) gene. The testosterone-dependent nuclear accumulation of polyglutamine-expanded AR protein is central to the pathogenesis. This hypothesis is supported by pre-clinical studies showing that testosterone deprivation ameliorates motor neuron degeneration in animal modes of SBMA. In a randomized placebo-controlled multi-centric clinical trial, leuprorelin, which suppresses secretion of testosterone, showed no definite effect on motor functions, although there was the improvement of swallowing function in a subgroup of patients whose disease duration was less than 10 years. Elucidation of the entire disease mechanism, early initiation of therapeutic intervention, and sensitive outcome measures to evaluate drug effect appear to be the key to a successful translational research on SBMA.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Banno
authors.forename: Keisuke
authors.initials: K
authors.lastname: Suzuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashizume
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Adachi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000818:Animals; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D015337:Multicenter Studies as Topic; D020966:Muscular Disorders, Atrophic / Q000188:drug therapy*; D057466:Nonsteroidal Anti-Androgens / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D057170:Translational Research, Biomedical
chemical_list: D057466:Nonsteroidal Anti-Androgens; D016729:Leuprolide