Fasudil bypasses genetic cause of spinal birth defect

07 Mar 2012

Spinal muscular atrophy (SMA) is an incurable, and progressive, disease caused by an inheritable defect in the gene SMN1. Depending on the severity of the mutation it can result in the loss of spinal cord motor neurons, muscle wasting (atrophy) and even death of an affected child. A new study published in Biomed Central's open access journal BMC Medicine shows that Fasudil, a ROCK inhibitor, can improve both the size of muscle fibers and their connection to motor neurons. Fasudil also increased the lifespan and improved the movement of SMA mice.

SMA affects 1 in 6,000 births and is the leading cause of death in young children. In its less severe form the muscle wasting of SMA traps bright young children within their bodies. Researchers from the Ottawa Hospital Research Institute and the University of Ottawa realized that SMA caused problems in regulation of the ROCK intracellular signaling pathway and that inhibiting this pathway could increase the lifespan of SMA mice.

By targeting the ROCK pathway in spinal cord and muscles, Fasudil bypasses the genetic defect SMN1. Dr Kothary, who led the team, explained, "Fasudil increased the lifespan of SMA mice from 30 to 300 days, allowing them to survive well into adulthood. Although it had no apparent effect on the damaged neurons themselves, Fasudil increased muscle size and the endplate junction between muscles and their motor neurons. Consequently, the mice were also better coordinated, better groomed, and could move about more freely than untreated SMA mice."

Melissa Bowerman from the Ottawa Hospital Research Institute continued, "Finding a cure for SMA is still a long way off, however we hope that treatment with drugs like Fasudil, which goes some way towards restoring normal developmental, or HDAC inhibitors, which alter how genes are regulated, along with nutrition and physiotherapy will provide a package of therapy to improve the quality and length of life of SMA children."

-ENDS-

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Notes to Editors

1.    Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy
Melissa Bowerman, Lyndsay M Murray, Justin G Boyer, Carrie L Anderson and Rashmi Kothary
BMC Medicine 2012, 10:24 doi:10.1186/1741-7015-10-24

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2.    BMC Medicine - the flagship medical journal of the BMC series - publishes original research articles, commentaries and reviews in all areas of medical science and clinical practice. To be appropriate for BMC Medicine, articles need to be of outstanding quality, broad interest and special importance. BMC Medicine (ISSN 1741-7015) is indexed/tracked/covered by PubMed, MEDLINE, BIOSIS, CAS, EMBASE, Scopus, Current Contents, Thomson Reuters (ISI) and Google Scholar.