October 16, 2003
The National Multiple Sclerosis Society
Researchers are using advanced technology to design vaccines to treat EAE, an MS-like disease in mice. William H. Robinson, MD, PhD, Lawrence Steinman, MD (Stanford University, CA) and colleagues report the results of a novel study in Nature Biotechnology (2003 Sep;21(9):1033-1039).
Research has indicated that “epitope spreading” may play a role in the immune attack on nerve-insulating myelin in MS. This means that although one protein in myelin may trigger the attack, the resulting immune response may spread to additional segments of that protein or other proteins. Understanding how epitope spreading occurs will be important in developing possible vaccines for use in treating MS.
In this study, the investigators have used a large-scale study of proteins – known as proteomics – to track the evolution of B-cell responses in mice with EAE. B-cell responses to triggering proteins have been implicated in autoimmune diseases such as diabetes and lupus, and there is evidence they play a role at some point in the course of MS. Using advanced technology called microarrays, they were able to study B-cell responses to more than 2,000 myelin protein molecules at once.
The results showed that mice with the most diverse B-cell responses – meaning that the B cells reacted to many protein molecules – experienced the largest number of relapses. These relapses were also associated with epitope spreading. Using this information, the investigators designed customized DNA vaccines containing “cocktails” of the genetic material that instructs several myelin proteins, which would induce maximal immune system “tolerance.” The vaccines succeeded in reducing relapse rates in the mice, as well as epitope spreading.
In an accompanying editorial, Eli Sercarz, PhD (Torrey Pines Institute
for Molecular Studies, San Diego) suggests that further studies are needed
to establish the usefulness of these exciting results in devising therapies
for people with MS. Bayhill Therapeutics, a company that has licensed therapeutic
compounds from the Stanford team, notes in a press release (August 10,
2003) that it plans to enter clinical studies in 2004 with a therapy for
Copyright © 2003, The National Multiple Sclerosis Society