title: Spinal muscular atrophy--recent therapeutic advances for an old challenge.
abstract: In the past decade, improved understanding of spinal muscular atrophy (SMA) aetiopathogenesis has brought us to a historical turning point: we are at the verge of development of disease-modifying treatments for this hitherto incurable disease. The increasingly precise delineation of molecular targets within the survival of motor neuron (SMN) gene locus has led to the development of promising therapeutic strategies. These novel avenues in treatment for SMA include gene therapy, molecular therapy with antisense oligonucleotides, and small molecules that aim to increase expression of SMN protein. Stem cell studies of SMA have provided an in vitro model for SMA, and stem cell transplantation could be used as a complementary strategy with a potential to treat the symptomatic phases of the disease. Here, we provide an overview of established data and novel insights into SMA pathogenesis, including discussion of the crucial function of the SMN protein. Preclinical evidence and recent advances from ongoing clinical trials are thoroughly reviewed. The final remarks are dedicated to future clinical perspectives in this rapidly evolving field, with a broad discussion on the comparison between the outlined therapeutic approaches and the remaining open questions.
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation, Neurology Unit, IRCCS Foundation Ca'Granda Ospedale Maggiore Policlinico, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Faravelli
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation, Neurology Unit, IRCCS Foundation Ca'Granda Ospedale Maggiore Policlinico, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Nizzardo
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation, Neurology Unit, IRCCS Foundation Ca'Granda Ospedale Maggiore Policlinico, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy.
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation, Neurology Unit, IRCCS Foundation Ca'Granda Ospedale Maggiore Policlinico, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003937:Diagnosis, Differential; D006801:Humans; D009046:Motor Neurons; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D016376:Oligonucleotides, Antisense / Q000235:genetics; D055532:SMN Complex Proteins / Q000235:genetics*
chemical_list: D016376:Oligonucleotides, Antisense; D055532:SMN Complex Proteins