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PMID: 25986506 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Spinal muscular atrophy--recent therapeutic advances for an old challenge.

Nature reviews. Neurology ·Vol. 11 ·No. 6 ·2015-06-00 ·Pages 351-9

Faravelli I, Nizzardo M, Comi GP, Corti S

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.

MeSH Terms
Animals Clinical Trials as Topic Diagnosis, Differential Humans Motor Neurons Muscular Atrophy, Spinal/diagnosis,genetics,therapy Oligonucleotides, Antisense/genetics SMN Complex Proteins/genetics
Chemicals
Oligonucleotides, Antisense SMN Complex Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Faravelli Irene
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.
Nizzardo Monica
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.
Comi Giacomo P
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.
Corti Stefania
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.
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Article Info
Journal
Nature reviews. Neurology
Abbr.
Nat Rev Neurol
ISSN
1759-4766
DOI
10.1038/nrneurol.2015.77
Published
2015-06-00
Epub
2015-00-19
Pages
351-9
Language
English
Region
England
NLM ID
101500072
Subset
IM
Grants
Telethon · GGP14025 · Italy
External Links
PubMed source DOI: 10.1038/nrneurol.2015.77 View journal details
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