Motor neurons are assembled and
maintained by the SMN protein,
but a genetic defect in the SMN1 gene can lead to spinal
muscular atrophy (SMA), an incurable and inheritable disease which
progresses during the lifetime of the patient.
The disease affects adults as well as children, and is the most common genetic cause of
infant mortality. SMA occurs in approximately
6,500 births, and even in less severe forms it greatly affects the quality
of life due to weakness and wasting of voluntary muscles.
This degenerative disease is characterized
by the loss of spinal cord motor neurons, and various therapeutic strategies are
being tested to prolong the survival of affected neurons in SMA patients. One
has been recently been published in BMC
Medicine by Melissa Bowerman and colleagues from the Ottawa Hospital
Research Institute and the University of Ottawa.
The team previously
found that the intracellular signalling pathway of the actin cytoskeleton regulator, RhoA/Rho
kinase (ROCK) is misregulated in animal models of SMA. In this current study,
the authors inhibited the ROCK pathway with Fasudil, and remarkably the
lifespan of the SMA mice was significantly increased from 30 to 300 days.
Administration with Fasudil also increased muscle fiber size and endplate
junction between muscles and their motor neurons, which therefore enabled these
mice to be better coordinated than the untreated SMA mice.
This work highlights the potential for muscle-specific targets for SMA
therapy, and the ROCK pathway as a therapeutic target for SMA pathogenesis. Moreover,
considering that Fasudil has already been approved by the US Food and Drug Administration
(FDA) for clinical trials of
other disorders, it represents a potentially valid therapy for this