Joel Chamberlain, research assistant professor in the department of medicine at the University of Washington in Seattle, was awarded an MDA research grant totaling $330,780 over three years to study a therapeutic approach called RNA interference (RNAi) for the treatment of facioscapulohumeral muscular dystrophy (FSHD).
"Despite the surprising complexity of the FSHD disease pathway, several lines of research converge to identify DUX4 protein production as the final step in the disease pathway," Chamberlain says.
Now, Chamberlain and colleagues are working to develop a therapy that targets production of DUX4 through interaction with DUX4 messenger RNA, or mRNA. (RNA is a chemical cousin to DNA and is involved in a chain of steps between DNA and cellular protein production.)
"To carry out RNAi, we will use an RNA that specifically binds to the DUX4 mRNA and directs the cell to destroy the target DUX4 mRNA," Chamberlain explains. "Once inside the muscle, the RNA made to carry out RNAi is produced continuously to treat disease and is expected to remain active for many years."
The team also is working to create a mouse model of FSHD that mimics the human disease. The investigators will use the model — as well as new cell and mouse models from collaborating laboratories — to test their DUX4 RNAi approach. They plan to make the model available to other researchers for the testing of additional potential therapies.
"We have developed this targeted approach, referred to as RNA interference or RNAi, to reverse disease," Chamberlain says. "It works well in mouse models of muscular dystrophies, and we are the only laboratory to have succeeded in changing the course of the disease by delivering this therapy to all the muscles of the mouse with a single intravascular (into a blood vessel) injection."
Funding for this MDA grant began Aug. 1, 2012.