From Gene to Therapy in Spinal and Bulbar Muscular Atrophy: Are We There Yet?

The document from April 2018 reviews the genetic causes, pathogenesis, and potential treatments for spinal and bulbar muscular atrophy (SBMA), a neuromuscular condition caused by abnormal expansions in the androgen receptor (AR) gene. It explains how the disease leads to muscle weakness and atrophy, and discusses the role of heat shock proteins and post-translational modifications of AR in disease progression. The paper also explores therapeutic strategies, including androgen deprivation, gene silencing, and targeting muscle tissue, but notes that no disease-modifying treatment was available at the time. Clinical trials had been conducted with mixed results, and while preclinical models showed promise with certain small molecules and RNA interference strategies, challenges remained in translating these findings into effective treatments for patients. The document concludes that further research is needed to understand SBMA's molecular mechanisms and to develop successful therapies.