Partnership Leads to Treatment for Rare Gum Disease

17 Apr 2017
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George Hajishengallis, DDS, PhD, the Thomas W. Evans Centennial Professor in Penn Dental’s Department of Microbiology George Hajishengallis, DDS, PhD, the Thomas W. Evans Centennial Professor in Penn Dental’s Department of Microbiology

A partnership between a professor at the Penn School of Dental Medicine and a scientist at the National Institute of Dental and Craniofacial Research (NIDCR) has led to a successful treatment for a rare genetic disorder called leukocyte adhesion deficiency (LAD) that leads to recurrent bacterial infections, gum disease, and lost teeth early in life. The disease arises because of an inability of neutrophils, a type of immune cell, to exit the bloodstream.

“This is really exciting because we see that a treatment performed in mice in our laboratory directly paved the way to a novel treatment for a serious disease that was not responsive to any other treatments,” said George Hajishengallis, DDS, PhD, the Thomas W. Evans Centennial Professor in Penn Dental’s Department of Microbiology.

As Hajishengallis was studying a mouse model of periodontitis, he found a strain of mice that had striking bone loss at a very young age. He later discovered that these mice had the mouse form of LAD. Also, their gum disease likely was attributable to very high levels of the signaling molecule interleukin-17 (IL-17), which leads to damaging inflammation. Yet the disease was inhibited when Hajishengallis used an antibody to block the activity of IL-17 or IL-23, a molecule required for IL-17 production.

During a scientific conference in 2012, Hajishengallis met Niki Moutsopoulos of the NIDCR, who had made similar observations in human LAD. Together, they realized that partnering could lead to important advances in LAD understanding and treatment. In 2014, they published their first joint paper, proposing that inhibition of the IL-23/IL-17 pathway could be an effective treatment for LAD. 

Now, the researchers have used a medication that previously had been approved by the Food and Drug Administration for psoriasis that blocks the activity of IL-23 and IL-12, another signaling molecule in treating a 19-year-old patient with LAD who had severe periodontitis and a chronic, nonhealing wound. After a year of treatment, the patient’s oral health and skin wound—which shared similar features of the immune malfunction as his gums—both dramatically improved.

“We used a mouse model of naturally occurring periodontitis that is very similar to human disease,” said Hajishengallis. “When you have a mechanism that causes almost exactly the same disease in 2 different species, it increases the chances of a treatment that would work in mice also working in a human.”

The study, “Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1,” was published by The New England Journal of Medicine.

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