Multiple Sclerosis Flares Blocked in Mice Models Using Protein Treatment

Therapies targeted toward a specific susceptible gene may be beneficial to multiple sclerosis (MS) patients, according to research published in Molecular Psychiatry.

Researchers from the University of Pennsylvania observed a key protein called Del-1 in mice models of MS, which has been previously found to prevent inflammation and bone loss in mice models of gum diseases. The protein demonstrated in previous studies conducted by the researchers that it acts as a regulator of immune cells like neutrophils and reduces inflammation. The body needs neutrophils to respond to infection and injury, but in autoimmune diseases like MS, too many accumulate and the inflammation is damaging. When the team applied a Del-1 treatment to gum tissue affected by periodontitis, the gums were protected against these adverse events.

In this study, the investigators observed Del-1 expression in brain tissue from deceased human MS patients. They concluded patients with chronic active MS lesions showed reduced Del-1 expression compared to healthy brain tissue and MS patients in remission at the time of their death. In animal models of MS, Del-1 expression was reduced in the spinal cords of the mice.

“We see that two completely different disease entities share a common pathogenic mechanism,” an author of the study, George Hajishengallis, DDS, PhD, said in a press release. “And in this case that means that they can even share therapeutic targets, namely Del-1.”

The next step of the research was to engineer mice models that lack Del-1 or expressed Del-1 in molecules of the immune system. Mice models which lacked Del-1 had more severe MS attacks and more damaging myelin. Mice without Del-1 with MS had increased numbers of inflammatory cells in their spinal cords at the height of the disease. Upon further review, this group of mice was also found to have increased levels of IL-17.

The mice were further observed — researchers had 1 more hypothesis they were hoping to test. They were curious to see what would happen when they replaced Del-1 to see if it would operate as a therapy. When the mice models of MS had an attack, similar to an MS flare-up in human patients, the researchers administered Del-1 treatment. The mice did not experience further episodes of their MS model.

In the future, the team will continue to study Del-1 expression to identify a subunit of the protein to determine which of them exactly has the same therapeutic effect.

“It’s amazing that our work in periodontitis have found application in a central nervous system disease,” Hajishengallis said. “This shows that periodontitis can be a paradigm for other medically important inflammatory diseases.”