Key Protein Reduces MS Severity In Mice

shutterstock_34558930Researchers from the University of Pennsylvania and other collaborators have discovered a key protein that may be able to reduce the severity of a disease in mice similar to multiple sclerosis in humans. The said protein, called Del-1 is known to be the same protein type that also prevents inflammation and bone loss in mice with gum disease. Results of the work can be found in the online journal Molecular Psychiatry.

Multiple sclerosis is a type of disease characterized by a dysfunctional immune system that begins to attack the body’s central nervous system. This leads to damaged nerve cells that result into symptoms that include mobility problems, cognitive impairments and others. Initially discovered with gum disease studies, the protein may indicate a common therapeutic benefit for other diseases, including MS. According to George Hajishengallis, a professor of microbiology in Penn’s School of Dental Medicine and an author on the study, “We see that two completely different disease entities share a common pathogenic mechanism. And in this case that means that they can even share therapeutic targets, namely Del-1.”

In earlier studies, Hajishengallis and his colleagues found out that Del-1 acts as a gatekeeper that blocks the accumulation of immune cells like neutrophils that can reduce inflammation. While the neutrophils may be essential in the body’s response to fight off infection or injury, over accumulation in tissues can result in inflammation and potential damage. Hajishengallis found that the Del-1 protein is also highly expressed in the brain. With its ability to reduce inflammation, the researchers hypothesized that Del-1 might be able to prevent inflammation in the central nervous system, just as it did in gum disease studies.

In order to test the theory, the researchers first looked into the expression of the Del-1 protein in brain tissues of people who have died from MS. The researchers found out that the Del-1 levels were reduced in the brain tissue compared to levels found in normal brain tissue or from MS patients who were found to be in remission at the time of their death. In addition, the researchers also found reduced Del-1 expression in the spinal cords of mice afflicted with the rodent equivalent of MS.

Having confirmed the association, researchers wanted to determine whether the reduction itself might play a role in disease development. The researchers worked with mutant mice models that either lacked Del-1 or Del-1 together with other molecules found in the immune system. They discovered that mice lacking Del-1 experienced more severe attacks of experimental autoimmune encephalomyelitis or EAE compared to normal mice. Mice without Del-1 that were induced to develop EAE also showed higher numbers of inflammatory cells in their spinal cords.

To further determine the effects of Del-1, the researchers waited until mice experienced an EAE attack, similar to a flare-up of MS in human patients. During the said attack, the researchers administered Del-1. Results showed that the mice did not experience further episodes of the disease.

According to Triantafyllos Chavakis from Germany’s Technical University Dresden, a senior author of the said study who collaborated with Hajishengallis, “This treatment prevented further disease relapse. Thus, administration of soluble Del-1 may provide the platform for developing novel therapeutic approaches for neuroinflammatory and demyelinating diseases, especially multiple sclerosis.”

The researchers are currently undergoing further study in trying to identify a subunit of the said protein that may also exhibit the same therapeutic effect on MS.

Source: University of Pennsylvania. (2014, November 11). Key protein can reduce severity of disease equivalent to multiple sclerosis in mice. ScienceDaily. Retrieved November 12, 2014 from www.sciencedaily.com/releases/2014/11/141111142241.htm

 
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