Strategies to fight muscle-fiber fragility have the potential to treat many forms of muscular dystrophy
We hear a lot these days about genes being destiny, about what can and can’t be done to go beyond predetermined biological limits.
A child born with a mutation in the gene for the muscle protein dystrophin, for instance, is destined to develop Duchenne or Becker muscular dystrophy, depending on the precise mutation and other factors.
Similarly, a child whose genetic heritage leads to a deficiency of the proteins laminin 2 or one of the sarcoglycans is almost certain to develop congenital or limb-girdle muscular dystrophy, respectively.
But all muscular dystrophies, regardless of their precise genetic origin, have at least one thing in common: fragile or flawed skeletal muscle fibers in which, over time, damage and degeneration outpace repair and regeneration. And this common feature may be an opportunity to change the “destiny” of muscle disease.
There are a variety of strategies being used in the quest to treat or cure muscular dystrophy. One strategy is to correct the basic genetic defect, either by inserting new, functional genes or by repairing existing genetic information. MDA is pursuing these gene therapy strategies avidly.
Other strategies include inserting healthy muscle stem cells that would contribute to the repair and regeneration process in muscle fibers; and stimulating muscle tissue to make more repair cells. Those strategies also are high among MDA’s funding priorities.
But there may be another way to change the fate of a muscle fiber that’s affected by a muscular dystrophy: redirecting some of the damaging processes that occur as a result of a variety of genetic mutations. Many of those processes are common to multiple forms of muscle disease.
For instance, what if you could put a brake on a normal protein that limits muscle regeneration? What if doing that also could keep an injured muscle fiber from forming so much scar tissue? Or, what if blood flow to contracting muscles could be increased, to improve exercise tolerance and reduce injury?
These and other strategies for protecting and building muscle are described in the following articles, through the eyes of the researchers who have devoted their careers to studying them.
Note: Although the research highlighted in these articles relied on the readily available and well-described dystrophin-deficient “mdx” mouse (a model of human Duchenne muscular dystrophy), none of the muscle-preserving approaches described is necessarily specific to DMD. Rather, this research has application for many forms of muscular dystrophy and perhaps even other muscle diseases.
As MDA grantee Eric Hoffman puts it, “The primary defect is not the be-all and end-all to everything. It’s the initiation of a process, and it’s the process — all the things that happen ‘downstream’ of the genetic defect — that really affects the patient.”