Targeted DNA vaccine may reverse disease.

2003 SEP 3 - (NewsRx.com & NewsRx.net) -- Stanford University Medical Center researchers have developed a way to tailor therapies to combat the specific inappropriate responses of autoimmune diseases in mice. The researchers also have shown that their technique can provide information needed to predict a disease's progression.

Eventually, their work may provide a way to reverse the course of such autoimmune diseases in humans as multiple sclerosis, rheumatoid arthritis and type 1 diabetes by first identifying the immune system culprits gone awry and then creating customized therapies for individual patients.

Researchers Bill Robinson, P.J. Utz and Lawrence Steinman published results last year showing how microarrays - glass slides spotted with minute amounts of the proteins against which the body may be reacting - can provide a profile of the antibodies' targets. Their current work, which appears in the September 2003 issue of Nature Biotechnology, takes the technology a step further and shows that the pattern of antibody activation can be used to predict and treat animals suffering from a disease resembling MS.

"Ultimately, we think the array can be used to guide patient-specific therapy," said Robinson, MD, PhD, assistant professor of medicine (immunology and rheumatology) and lead author of the study. For example, a blood sample from a patient thought to have MS could be profiled using the array to help identify whether the person is likely to progress to full-blown disease and whether the individual would benefit from therapy. The information obtained in the profile could then be used to personalize therapies.

The team, which included former Stanford researcher Hideki Garren, MD, PhD, showed that this strategy works in a mouse model of MS called experimental autoimmune encephalomyletis, or EAE. In both conditions, the immune system launches an attack against the myelin sheath, the fatty cells that insulate neurons from electricity and ensure the speedy transmission of nerve impulses. Neurons that have patches of myelin destroyed by MS or EAE short-circuit and can lead to a variety of neurological disorders, depending on the part of the brain affected.

"Looking at one MS marker at a time had previously not been terribly informative," said Robinson. "We thought that looking at thousands at once would be more fruitful." Thanks to a dozen or so labs around the world that shared their protein samples, the group rapidly produced a comprehensive array that covered hundreds of the myelin sheath proteins.

When they analyzed serum samples from EAE mice using the array, they found that each mouse had a unique pattern of reactivity. Based on their antibody profiles, mice whose immune systems were attacking more elements on the myelin sheath progressed to a more severe disease, while mice whose immune systems made more restricted responses did not progress and had fewer flare-ups. The group then designed a treatment to reverse the progression of the disease, treating mice that had already suffered an initial attack of paralysis.