sábado, 29 de abril de 2017

Penn Dental research leads to treatment for rare gum disease | Penn Current

Penn Dental research leads to treatment for rare gum disease | Penn Current

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Penn Dental research leads to treatment for rare gum disease



The New England Journal of Medicine ©2017

A partnership between a School of Dental Medicine professor and a scientist at the National Institutes of Health, sparked by a chance meeting, has led to a successful new treatment for a rare genetic disorder.
“This is really exciting because we see that a treatment performed in mice in our laboratory directly paved the way to a novel clinical treatment for a serious disease that was not responsive to any other treatments,” says George Hajishengallis, the Thomas W. Evans Centennial Professor in Penn Dental’s Department of Microbiology.
Hajishengallis has spent much of his career studying periodontitis, a form of chronic gum disease characterized by microbe-driven inflammation of the tissues and bone that support the teeth. In the course of his research in a mouse model of periodontitis, he came across a strain of mice that had striking bone loss at a very young age.
Upon further investigation, he realized that these animals had essentially the mouse form of a human disease called leukocyte adhesion deficiency, or LAD. Individuals with this rare genetic disorder experience recurrent bacterial infections and terrible gum disease, often losing their teeth early in life. The disease arises because of an inability of neutrophils—a type of immune cell—to exit the bloodstream.
Hajishengallis noted that the gum disease of LAD mice was likely attributable to very high levels of the signaling molecule IL-17, which leads to damaging inflammation. The disease was inhibited when Hajishengallis and colleagues used an antibody to block the activity of IL-17 or IL-23, a molecule required for IL-17 production.
George Hajishengallis
George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Microbiology at Penn Dental. Photo by Penn Dental
These data were unpublished, but during a scientific conference in 2012, Hajishengallis met Niki Moutsopoulos of the National Institute of Dental and Craniofacial Research (NIDCR), a researcher who had made similar observations in human LAD. The two realized that partnering together could lead to important advances in LAD understanding and treatment.
They published their first joint paper in 2014 in Science Translational Medicine proposing that inhibition of the IL-23/IL-17 pathway could be an effective treatment of LAD disease.
A recent report in the New England Journal of Medicine, on which Moutsopoulos is first author and Hajishengallis a coauthor, describes the fruits of this partnership, supported with funding from NIDCR. Using a drug that had previously been FDA-approved for psoriasis that blocks the activity of IL-23 as well as another signaling molecule, IL-12, the authors described treating a 19-year-old patient with LAD who had severe periodontitis and a chronic, non-healing wound.
Though they had hoped to perhaps improve this patient’s gum disease, after a year of treatment, not only did his oral health dramatically improve, but so did his skin wound, which shared similar features of immune malfunction as his gums.
While much has been reported about the failure of mouse models to translate to human therapies, Hajishengallis was gratified that, in this case, the treatment worked in both species.
“We use a mouse model of naturally occurring periodontitis that is very similar to human disease,” says Hajishengallis. “When you have a mechanism that causes almost exactly the same disease in two different species, it increases the chance of a treatment that would work in mice also working in a human.”
Originally published on Thursday, April 6, 2017.

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