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Neural Plasticity
Volume 2012, Article ID 456478, 13 pages
http://dx.doi.org/10.1155/2012/456478
Review Article

Therapy Development for Spinal Muscular Atrophy in SMN Independent Targets

1Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan
2Department of Neurology, National Taiwan University Hospital, Yun-lin Branch, Yun-lin 64041, Taiwan

Received 1 March 2012; Revised 5 April 2012; Accepted 6 April 2012

Academic Editor: Hansen Wang

Copyright © 2012 Li-Kai Tsai. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder, leading to progressive muscle weakness, atrophy, and sometimes premature death. SMA is caused by mutation or deletion of the survival motor neuron-1 (SMN1) gene. An effective treatment does not presently exist. Since the severity of the SMA phenotype is inversely correlated with expression levels of SMN, the SMN-encoded protein, SMN is the most important therapeutic target for development of an effective treatment for SMA. In recent years, numerous SMN independent targets and therapeutic strategies have been demonstrated to have potential roles in SMA treatment. For example, some neurotrophic, antiapoptotic, and myotrophic factors are able to promote survival of motor neurons or improve muscle strength shown in SMA mouse models or clinical trials. Plastin-3, cpg15, and a Rho-kinase inhibitor regulate axonal dynamics and might reduce the influences of SMN depletion in disarrangement of neuromuscular junction. Stem cell transplantation in SMA model mice resulted in improvement of motor behaviors and extension of survival, likely from trophic support. Although most therapies are still under investigation, these nonclassical treatments might provide an adjunctive method for future SMA therapy.