title: Spinal muscular atrophies.
abstract: Spinal muscular atrophies (SMA) are genetic disorders characterized by degeneration of lower motor neurons. The most frequent form is caused by mutations of the survival motor neuron 1 gene (SMN1). The identification of this gene greatly improved diagnostic testing and family-planning options of SMA families. SMN plays a key role in metabolism of RNA. However, the link between RNA metabolism and motor neuron degeneration remains unknown. A defect in mRNA processing likely generates either a loss of function of some critical RNA or abnormal transcripts with toxic property for motor neurons. Mutations of SMN in various organisms highlighted an essential role of SMN in motor axon and neuromuscular junction development or maintenance. The quality of life of patients has greatly improved over recent decades through the improvement of care and management of patients. In addition, major advances in translational research have been made in the field of SMA. Various therapeutic strategies have been successfully developed aiming at acting on SMN2, a partially functional copy of the SMN1 gene which remains present in patients. Drugs have been identified and some are already at preclinical stages. Identifying molecules involved in the SMA degenerative process should represent additional attractive targets for therapeutics in SMA.
authors.affiliation: Hôpital Necker-Enfants Malades and Université Paris Descartes, Paris, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Viollet
authors.forename: Judith
authors.initials: J
authors.lastname: Melki
mesh_terms: D002648:Child; D006801:Humans; D015994:Incidence; D009046:Motor Neurons / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000628:therapy*; D009410:Nerve Degeneration / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010641:Phenotype