History review of spinal muscular atrophy

Spinal muscular atrophy is a neuromuscular disorder caused by the degeneration of alpha motoneurons in the spinal cord. This autosomal recessively inherited disease manifests with progressive muscular atrophy and weakness. First attempts to diagnose this condition date back to the late 19th century. At that time, many researchers tried to understand the aetiology of these unusual symptoms and to describe for the first time a previously unknown disease entity. Werdnig, Hoffman, Thomson and Beevor have shown the specific clinical picture of spinal muscular atrophy by noticing its hereditary nature. Further observations allowed to create a classification system for different types of spinal muscular atrophy and to conduct genetic research to identify the underlying molecular mechanisms. In the late 1990s, Gillian's team discovered SMN gene location. This provided an opportunity to initiate clinical trials into targeted treatment. Many strategies have been used, such as increasing SMN protein levels, modifying invalid splicing or modifying calcium release with troponin regulatory complex. These studies helped develop therapies, such as nusinersen, onasemnogene abeparvovec or risdiplam, which were subsequently approved by the Food and Drug Administration. This review shows a historical timeline of spinal muscular atrophy, highlighting the important milestones in its discovery.