Understanding the environmental and genetic risk factors involved in multiple sclerosis is a major challenge when it comes to designing effective treatments. Researchers at the University of California, Irvine, have produced data that may point the way forward for personalized therapies for the disease. Michael Demetriou, associate director of the UC Irvine Multiple Sclerosis Research Center, has analyzed samples from roughly 13,000 people and identified how environmental factors, like the metabolism and vitamin D3 levels, interact with the genes interleukin-7 receptor-α, interleukin-2 receptor-α, MGAT1, and CTLA-4. Previous research by Demetriou on mice revealed adding specific sugars to proteins cause a spontaneous MS-like disease. Through simple genotyping, Demetriou hopes physicians will someday be able to reverse the genetic-induced defects with vitamin D3 or the simple sugar N-acetylglucosamine, he says.
"Our data indicates that specific combinations of genetic and environmental risk factors lead to defects in protein glycosylation, thereby promoting multiple sclerosis," Demetriou says. "Thus, we can predict, based on genotyping, which patients are most likely to benefit from this type of therapy, which we also show inhibits MS-like disease in mice by altering protein glycosylation."
One of the primary reasons that this area of MS research has remained unexplored is that protein glycosylation is a still an under-studied field. "Very few medical researchers understand protein glycosylation despite the fact that virtually all cell surface and secreted proteins are modified by the addition of sugars and that this imparts critical non-genome encoded information to the protein that alters cell function," he says.
Moving forward, Demetriou plans to investigate the roughly 30 genes already known to regulate protein glycosylation, which may also harbor polymorphisms that promote MS. "It is likely that we have uncovered only the tip of the iceberg and that there are many yet to be discovered genetic factors that also alter protein glycosylation to promote MS and other autoimmune diseases," he says. "We are currently vigorously investigating this possibility and are planning to move forward with a clinical trial of N-acetylglucosamine alone and in combination with vitamin D3."