Rinsho Shinkeigaku (Clinical Neurology)

Symposium 3

Anti-androgen therapy for spinal and bulbar muscular atrophy (SBMA)

Masahisa Katsuno, M.D.1), Haruhiko Banno, M.D.1)2), Keisuke Suzuki, M.D.1), Atsushi Hashizume, M.D.1), Hiroaki Adachi, M.D.1), Fumiaki Tanaka, M.D.1)3) and Gen Sobue, M.D.1)

1)Department of Neurology, Nagoya University Graduate School of Medicine
2)Institute for Advanced Research, Nagoya University
3)Department of Neurology, Medical Center, Yokohama City University

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 polyglutamineexpanded 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.
Full Text of this Article in Japanese PDF (270K)

(CLINICA NEUROL, 52: 1207|1209, 2012)
key words: spinal and bulbar muscular atrophy (SBMA), leuprorelin acetate, clinical trial, translational research, endpoint

(Received: 25-May-12)