New Routes to Therapy for Spinal and Bulbar Muscular Atrophy

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a genetically inherited neuromuscular disorder characterized by loss of lower motor neurons in the brainstem and spinal cord and skeletal muscle fasciculation, weakness, and atrophy. SBMA is caused by expansion of a polyglutamine (polyQ) tract in the gene coding for the androgen receptor (AR). PolyQ expansions cause at least eight other neurological disorders, which are collectively known as polyQ diseases. SBMA is unique in the family of polyQ diseases in that the disease manifests fully in male individuals only. The sex specificity of SBMA is the result of the interaction between mutant AR and its natural ligand, testosterone. Here, we will discuss emerging therapeutic perspectives for SBMA in light of recent findings regarding disease pathogenesis.