Drug discovery for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessively inherited neuromuscular disorder with an early lethal outcome for > 50% of all patients. Today, there is no therapy for SMA available. SMA patients fail to produce the functional survival motor neuron 1 (SMN1) protein, but have variable numbers of SMN2 copy genes that have a major effect on the disease severity. A quite significant number of drugs have been identified, so far, which are able to activate the transcription, restore the correct SMN2 splicing or stabilize the SMN2 protein. Some of these drugs have been shown to be beneficial and to increase SMN2 protein levels in SMA patients. The clear proof given by placebo-controlled clinical trials is still pending. Nevertheless, SMA may be the first inherited disorder in which the activation/splicing correction of a copy of the gene may cure or ameliorate the disease.