image: This is John Lukens, Ph.D. view more
Credit: Josh Barney | University of Virginia Health System
New research into the causes of the excessive inflammation that drives multiple sclerosis has identified a faulty "brake" within immune cells, a brake that should be controlling the inflammation. This points to a potential target for developing new therapies to treat multiple sclerosis and could have important implications for other autoimmune diseases, such as the colon disease colitis and the chronic skin condition atopic dermatitis.
Further, the work has produced new research models of multiple sclerosis symptoms such as movement disorders and balance control problems that have, until now, resisted efforts to mimic them effectively in the lab. These models represent important new tools in the efforts to better understand - and eventually cure - MS and other autoimmune conditions.
The researchers determined that a mutation in the gene Nlrp12 was causing immune cells known as T cells to go haywire. Normally, the researchers determined, the protein the gene produces acts as a brake within T cells to control the inflammatory response. But a mutation in that gene disrupts the natural process and provokes severe inflammation - with effects the researchers found most intriguing.
To the researchers' surprise, the resulting inflammation did not produce the paralysis often associated with multiple sclerosis. It did, however, produce other MS symptoms -- such as movement disorders and problems with balance control -- which scientists have struggled to replicate in experimental lab settings.
"It's important to note that MS is a spectrum disorder - some patients present with paralyzing conditions and some patients don't," said researcher John Lukens, PhD, of the University of Virginia School of Medicine Department of Neuroscience and its Center for Brain Immunology and Glia. "Not everybody's symptoms are the same, so this might give us a glimpse into the etiology or pathogenesis of that family of MS."
By blocking the inflammatory response, doctors may one day be able to control the symptoms it causes, both in MS and in other diseases driven by hyperinflammation.
The findings have been published online by the scientific journal Immunity: http://www.cell.com/immunity/abstract/S1074-7613(15)00120-X
###
The article was authored by Lukens, of UVA and formerly of St. Jude Children's Research Hospital; Prajwal Gurung, of St. Jude; Patrick J. Shaw, of St. Jude; Maggie J. Barr, of St. Jude; Md. Hasan Zaki, of the University of Texas Southwestern Medical Center; Scott A. Brown, of St. Jude; Peter Vogel, of St. Jude; Hongbo Chi, of St. Jude; and Thirumala-Devi Kanneganti, of St. Jude.
Journal
Immunity