George Hajishengallis, a professor of microbiology in the School of Dental Medicine, spends most of his professional energy on research that concerns the mouth; specifically, he studies a severe form of gum disease called periodontitis. But, as he notes, “the mouth is not an isolated entity.” 

In a paper published this week in the journal Molecular Psychiatry, his work has found application in treating the rodent equivalent of multiple sclerosis (MS). A molecule called Del-1 that Hajishengallis and others have found to block inflammation in the gums also puts a stop to the recruitment of certain inflammatory cells in the central nervous system, and brought a halt to the symptoms of disease in mice.

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

Hajishengallis and his collaborators began the work with a couple of clues that Del-1 might play a role in regulating inflammation not only in the gums, but also in the central nervous system. First, Del-1 is highly expressed in the brain. And second, mutations in Del-1 have been found to be potentially linked with an increased risk of both MS and Alzheimer’s disease.

Looking at brain tissue from people who died of multiple sclerosis, they found Del-1 levels were reduced in people with chronic active MS lesions. Del-1 levels were also lower than normal in mice with a disease akin to MS called experimental autoimmune encephalomyelitis (EAE).

Mice lacking Del-1 had more severe attacks of EAE than normal mice, more damage to their neurons, and more inflammatory cells in their spinal cords at the disease’s peak.

Further experiments showed that this inflammation could be linked back to the signaling molecule IL-17, which triggers the accumulation of inflammatory cells. Earlier studies by Hajishengallis showed that Del-1 blocks the activity of IL-17 in gum tissue, effectively reducing inflammation. The same proved true in the case of the central nervous system.

A final question was whether Del-1 given to sick mice could reduce the severity of EAE. When the mice had an attack of the disease, similar to a flare-up of MS in human patients, the researchers administered Del-1.

The Del-1 treatment appeared to stop the disease in its tracks. Mice that received Del-1 did not suffer another attack.

“We see that two completely different disease entities share a common pathogenic mechanism,” Hajishengallis says. “And in this case that means that they can even share therapeutic targets, namely Del-1.”