Human Molecular Genetics Advance Access originally published online on May 28, 2009
Human Molecular Genetics 2009 18(17):3145-3152; doi:10.1093/hmg/ddp253
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice
1 Department of Neurology and 2 Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA 3 Jackson Laboratory, Bar Harbor, ME, USA
* To whom correspondence should be addressed at: Department of Neurology, Johns Hopkins University, Meyer 5-119b 600 N. Wolfe Street, Baltimore, MD 21287, USA. Tel: +1 4105026085; Fax: +1 4109551961; Email: csumner1{at}jhmi.edu
Received April 17, 2009; Accepted May 22, 2009
There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-β family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn–/–) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA.