DMD Briefs: Stopping Inflammation on Earth and in Space

Inflammation exacerbates muscle destruction in Duchenne muscular dystrophy, and several investigators — including some on the International Space Station — are trying to block it

The limited-gravity environment on the International Space Station has aided the development of an anti-inflammatory compound for DMD.
Article Highlights:
  • Inflammation is a normal process the body uses to control the spread of infection; but in some situations, such as in Duchenne muscular dystrophy (DMD), it can do more harm than good.
  • Inflammation involves contributions from many molecules, providing researchers with several substances to block or enhance in order to lessen the impact.
  • Development of one anti-inflammatory compound for DMD has been aided by experimentation on the International Space Station.
by Margaret Wahl on September 13, 2012 - 4:27pm

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.

Research on space station has aided development of HQL-79

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.

Four MDA-supported anti-inflammation projects

  • In May 2012, the Association funded the Rockville, Md., biotechnology company ReveraGen to develop what it's dubbed a dissociative glucocorticoid to treat DMD. ReveraGen's experimental compound VBP15 is designed to have the desirable properties of corticosteroids without their undesirable effects.
  • In April 2012, MDA announced it would support Catabasis Pharamaceuticals in Cambridge, Mass., to develop and test experimental compounds that counter DMD-related inflammation without causing corticosteroid-type side effects. The company is working with two experimental compounds, dubbed CAT-1004 and CAT-1040, in a DMD research mouse.
  • Molecular biologist and MDA research grantee Melissa Spencer at the University of California, Los Angeles is targeting a protein called osteopontin, which appears to play a role in the inflammatory process in DMD.
  • Pura Muñoz-Canoves at Pompeu Fabra University in Barcelona, Spain, has MDA support to investigate the role of a protein called plasminogen activator inhibitor 1 (PAI-1) as a possible regulator of inflammation and scar tissue formation in DMD.
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