Developments in the discovery of drugs for spinal muscular atrophy: successful beginnings and future prospects.

INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in a gene that produces a protein called survival motor neuron (SMN). SMN has an important role in snRNP assembly in all cells but that may not be its only role; the reasons for SMN deficiency resulting in neuromuscular dysfunction and motor neuron degeneration remain active areas of research. Besides increasing SMN, compensating for SMN deficiencies or neuroprotection may be therapeutic options for SMA. Age of onset and the rate of disease progression are variable and therapeutic strategies should be appropriate to subtypes of SMA patients.

AREAS COVERED: The article discusses SMA, their targets and where these targets can be found. Additionally, the article reviews small molecules identified as disease modifiers and how these small molecules were discovered. The article also describes and discusses emerging concepts regarding the disease mechanisms. The author compiled this review using scientific literature, patent databases, company and patient association and government websites.

EXPERT OPINION: Small molecules targeting various processes implicated in SMA are reaching the clinic. These molecules and targets, although not yet validated, are providing insight into the complexity of a 'simple' genetic disease such as SMA. SMA is not a single disease and so various therapeutic strategies are needed. Biomarkers and regulatory guidelines are required to select patients for clinical trials, decide when to initiate treatment and how to develop combinations of investigational drugs.