While it has often been suspected that MS is the result of inherent risk factors ignited by an environmental trigger, a group of researchers from the UC Irvine MS Research Center have recently published data that points to the possible combination of events that causes the disease, and includes a theory that defines the importance of Vitamin D.
Using blood samples from about 13,000 people, study author Michael Demetriou, M.D., and colleagues identified the way environmental factors (including metabolism and vitamin D3 obtained through either sunlight exposure or diet) interact with four genes to affect how specific sugars are added to proteins regulating the disease. Those genes are interleukin-7 receptor-alpha, interleukin-2 receptor-alpha, MGAT1 and CTLA-4.
Earlier work on mice by Demetriou revealed that changes in the addition of these specific sugars to proteins creates a spontaneous MS-like disease. They also found that N-acetylglucosamine (GlcNAc), a dietary supplement and simple sugar related to glucosamine, is able to suppress this process.
The current research shows that both vitamin D3 and GlcNAc can reverse the effects of four human MS genetic factors and restore the normal addition of sugars to proteins. "This suggests that oral vitamin D3 and GlcNAc may serve as the first therapy for MS that directly targets an underlying defect promoting disease," Demetriou said.
Virtually all proteins on the surface of cells, including immune and nervous system cells, are modified with complex sugars of variable lengths and composition. This adds information to proteins separate from that directly defined by the genome. The sugars interact with specific sugar-binding proteins on the cell, forming a molecular lattice that controls the clustering, signaling and surface expression of critical receptors and transporters, such as the T cell receptor and CTLA-4. Reducing sugar modification weakens the lattice and enhances growth and activity of immune system T cells in such a way that they increase neural degeneration -- a hallmark of MS.
Production of the complex sugars is regulated by both metabolic and enzymatic functions, the latter altered by genetic MS risk factors and vitamin D3. Demetriou pointed out that the MGAT1 genetic variant linked to MS increases or decreases the sugars attached to proteins depending on metabolism -- one possible explanation for why people with the same genetic risk factor may or may not develop MS.