Researchers say the muscle-repair protein WNT7a may hold promise as a therapy for both Duchenne and Becker muscular dystrophies
Update (May 1, 2013): Fate Therapeutics announced at the MDA Scientific Conference held in Washington, D.C., in April, that it has developed a druglike compound based on WNT7a. At the conference and in an April 22, 2013, press release, the San Diego company said its new compound resulted in a signficant increase in strength in a mouse leg muscle, and that it plans to advance it to human studies.
Update (Dec. 20, 2012): This story has been updated to reflect the availability of a 12-minute podcast with researcher Michael Rudnicki, in which Rudnicki discusses the advantages and disadvantages of developing protein-based therapies (such as WNT7a) versus cell-based therapies to treat muscle disease.
Injecting a muscle-repair protein known as WNT7a into the muscles of mice lacking the dystrophin protein and showing a disease resembling Duchenne muscular dystrophy (DMD) significantly increased muscle strength and the size of muscle fibers, leading scientists to conclude that it could be developed into a treatment for DMD and the related disorder Becker muscular dystrophy (BMD). (DMD and BMD both result from dystrophin deficiency.)
|Michael Rudnicki, an MDA grantee at Ottawa Hospital Research Institute in Canada, led a research team whose findings suggest that WNT7a is a good candidate for development as a treatment for Duchenne muscular dystropy and possibly Becker MD.|
Michael Rudnicki, director of the Regenerative Medicine Program at Ottawa Hospital Research Institute (OHRI), Canada, received MDA support for these experiments, results of which were published Nov. 26, 2012, in Proceedings of the National Academy of Sciences (PNAS). The complete paper is available on the PNAS site without charge.
In a Nov. 27 press release from OHRI, Rudnicki called the restoration of muscle strength in the treated mice "unprecedented and dramatic."
The work was done in collaboration with San Diego-based biotechnology Fate Therapeutics, which specializes in developing pharmaceuticals based on stem cell biology. Rudnicki is among the founders of this company, which hopes to start a clinical trial of WNT7a for DMD in the near future.
In 2009, Rudnicki and others published findings showing that the WNT7a protein stimulates muscle repair by increasing the available supply of muscle satellite cells. These are muscle stem cells that lie near muscle fibers and are dormant until needed for repair or regeneration of fibers. When needed, they increase in number (proliferate) and mature (differentiate).
The new findings build on the earlier results. In addition to the significant increases in fiber strength and size, the researchers found that:
To investigate whether WNT7a signaling is the same in human and mouse muscles, the investigators also analyzed human muscle tissue from healthy male donors. They concluded that the protein’s effects in skeletal muscle are the same in humans as in mice.
"Our experiments provide compelling evidence that WNT7a treatment counteracts the significant hallmarks of DMD, including muscle weakness, making WNT7a a promising candidate for development as an ameliorative treatment for DMD," they wrote in the Nov. 26 paper.
They suggest that increasing muscle strength by injecting WNT7a into specific, vital muscle groups, such as those involved in breathing, should be considered as a therapeutic approach for this disease.