ABSTRACT
An entirely new frontier of biomedical research was created when La Spada et al. discovered that expansion of the CAG trinucleotide repeat encoding the polymorphic polyglutamine tract in the human androgen receptor was associated absolutely with the neurodegenerative disease spinobulbar muscular atrophy (SBMA). The typical course of SBMA (McKusick Catalogue MIM 313200) is slowly progressive atrophy (wasting) and weakness of the proximal musculature (the muscles of the pelvic and shoulder girdles) starting in the third to fifth decades. Arbizu et al. (1983) first suggested that hereditary AR failure involving mainly the spinal and bulbar motor neurons and germinal cells could cause SBMA. In fact, some of the clinical and laboratory features of male hypogonadism in these patients were eminently compatible with androgen insensitivity rather than androgen deficiency. Unravelling the pathogenetic pathway(s) in SBMA should lead to development of a rational treatment for SBMA.
