Inflammation exacerbates muscle destruction in Duchenne muscular dystrophy, and several investigators — including some on the International Space Station — are trying to block it
Inflammation — the immune system's first line of defense in tissue that's been damaged by injury or infection — is a good example of a process that's a good thing up to a point and under certain circumstances and a bad thing in excess or under the wrong circumstances.
The redness and swelling that results from a splinter in the finger may be painful, but it's part of the healing process. The dilated blood vessels and influx of cells from the immune system are an essential part of the body's damage control system, killing invading microbes before they travel through the bloodstream.
But sometimes the body's inflammatory responses are set in motion when it might have been better to have left well enough alone. For instance, there's increasing evidence that inflammatory responses exacerbate Duchenne muscular dystrophy (DMD).
In this disease, the absence of the dystrophin protein in muscle fibers — caused by any of a number of genetic mutations in the dystrophin gene — leaves the fibers with fragile, leaky membranes. The fibers undergo successive rounds of damage and repair over the years and are ultimately replaced by scar tissue.
Inflammation appears to hasten the damage and loss of muscle fibers, which may be why anti-inflammatory medications known as corticosteroids (glucocorticoids) slow the progression of DMD.
But corticosteroids, such as prednisone and deflazacort, don't stop the disease. They also have many undesirable side effects, such as weight gain and bone loss.
For that reason, a number of research groups, many of which have MDA support, are working on alternative anti-inflammatory strategies for DMD. Their goal is to develop drugs with a better benefit-to-risk ratio than corticosteroids.
Here are some of the approaches being taken to counteract inflammation and scarring in DMD-affected muscles.
In 2009, a group of researchers in Osaka, Japan, found that if they treated mice with a DMD-like disease with a compound called HQL-79, they could suppress inflammation and reduce cell death in muscle fibers. HQL-79, they found, interferes with the action of an enzyme called prostaglandin D synthase (article available for free download).
Investigating HQL-79 has — perhaps surprisingly — been one of the scientific research projects of the International Space Station.
The limited-gravity environment of the station allows chemical crystals to grow larger than they would on Earth, so scientists can study and modify their three-dimensional structures more easily.
The large, high-quality HQL-79 crystals grown in space have already led to the construction of a more potent version of this prostaglandin D synthase inhibitor, according to NASA's International Space Station website (see Duchenne's Muscular Dystrophy). This development increases the chance that HQL-79 could be developed into a drug to treat DMD.