Introduction to the Special Issue on Spinal and Bulbar Muscular Atrophy.

This special issue is dedicated to spinal and bulbar muscular atrophy (SBMA) and is based on the conference sponsored by the European Neuromuscular Centre (ENMC) held in March 2015. SBMA, also known as Kennedy's disease, is a neurodegenerative disease caused by an expansion of a repeat of the trinucleotide CAG encoding glutamine in the gene encoding androgen receptor (AR). Expansion of polyglutamine in the AR results in selective lower motor neuron degeneration and skeletal muscle atrophy. SBMA belongs to the family of polyglutamine diseases, which also includes Huntington's disease, dentatorubral-pallidoluysian atrophy, and spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17. Within the family of polyglutamine diseases, SBMA is unique in its gender-specificity, with full disease manifestation restricted to males. Since the disease is ligand (androgen)-dependent, SBMA manifests primarily in males which have high levels of circulating androgens in the serum; females are usually asymptomatic. Indeed, the polyglutamine-expanded AR is converted to a neurotoxic species upon binding to androgens. The mechanisms through which androgen binding triggers the disease are under investigation. Although several therapeutic strategies have been proposed to date, there is currently no effective therapy to arrest or delay disease progression in patients.