By JUDY SIEGEL
HAIFA (September 24) - An important and innovative method developed at the Technion using genetic engineering to "vaccinate" the body with DNA has proven itself successful in mice as a model for treating autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and type-I diabetes.
Dr. Nathan Karin and colleagues of the Rappaport Faculty of Medicine's department of immunology have just published an article on their research in the latest issue of Gene Therapy.
In autoimmune diseases, the body's immune system attacks tissue that it mistakenly recognizes as "enemy" or "foreign" and triggers an inflammatory process.
In MS, the myelin coating of neurons is attacked, causing the nervous system to short circuit, with resulting neurological damage; in rheumatoid arthritis, the connective tissue is harmed; while in juvenile-onset (insulin-dependent) diabetes, beta cells in the pancreas that produce insulin are destroyed.
Karin's team is the first to develop a genetic treatment that prevents the immune system from creating an inflammatory process when the body's own tissue is misidentified as foreign. The Technion technique, which has not yet been tested in humans, is unique in that it uses tools whereby the immune system attacks its own tissue to "re-educate" it and prevent it from causing harm.
Karin's group injected a viral vector (carrier agent) into which segments of DNA were engineered into the leg muscle of lab animals. Only about four or five injections were needed. These segments code for pro-inflammatory proteins connected to the auto-immune diseases.
Using this technique, which is called "naked DNA vaccination," the researchers succeeded in breaking down the passive immunity to some proteins important in the inflammatory process and create "immunity memory" against these substances. As a result, antibodies against the proteins are created, and the inflammatory process is quickly controlled. A Haifa scientific "incubator" will be established to complete the animal experiments and prepare for eventual clinical trials on patients.
Karin told The Jerusalem Post he has been working on the technique for three years, some of it as post-doctoral work at Stanford University in the US.
Prof. Irun Cohen, director of the Minerva Center for Research into Autoimmune Diseases at the Weizmann Institute in Rehovot, commented that the concept of naked DNA vaccination is "very significant. It's another example of how the immune system can be enlisted to regulate its own affairs. Using it on patients at this point would be very premature, as we don't know about side effects or if it would work in humans as it has in mice. We have to know more about the mechanisms.
"A possible problem could be that the technique knocks out the immune
response, but if you do this completely, the body could be susceptible
to infection from pathogens from the outside. It needs selective regulation
so that the immune system can still attack outside invaders. But down the
line, I have no doubt that Dr. Karin's approach will bring about important
therapeutic reagents and more knowledge."