HAIFA, Israel and NEW YORK, N.Y., August 2, 2000 -- A novel modification of a new technology born of genetic engineering, and known as naked DNA vaccination, holds the potential of overcoming autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
Under development by Dr. Nathan Karin of the Technion-Israel Institute of Technology, the vaccine is currently being successfully tested in animals. A paper on this technology appears in the August 1 issue of the Journal of Clinical Investigation.
In multiple sclerosis (MS) and rheumatoid arthritis (RA), the body essentially attacks itself causing inflammation. In MS, the myelin sheath of nerves falls victim, while in RA, it is the joints and cartilage that are attacked. The damage is done by small proinflammatory peptides called proinflammatory cytokines and chemokines.
Rheumatoid arthritis affects 2.1 million Americans, 1.5 million of whom are women, according to the Arthritis Foundation. Its symptoms include inflammation of joints, swelling, difficulty moving and pain. The National Multiple Sclerosis Society reports that nationwide, there are an estimated 250,000 to 350,000 people with MS, and that women are twice as likely to contract the disease as men. The symptoms of this chronic, often disabling disease of the central nervous system may be as mild as numbness in the limbs or severe to the point of paralysis or loss of vision.
"One way these diseases could be controlled is by immunizing patients with neutralizing antibodies directed against one or more of the proinflammatory peptides," says Karin. And, in fact, recent clinical trials have proven successful at inhibiting rheumatoid arthritis by using antibodies to counter inflammation causing cytokines.
There are, however, two key problems associated with using the neutralizing antibodies tested in the trials. First, they require frequent administration. Additionally, the body¹s immune system eventually recognizes the antibodies as foreign and generates an immune response that can exacerbate the disease.
It is to counter these undesirable effects that Karin has utilized naked DNA vaccination technology. This consists of introducing engineered genes based on the culprit peptides into the body. When the patient¹s immune system sees these genes as outside invaders, it produces its own neutralizing antibodies capable of restraining the disease. Essentially, the process involves "teaching the immune system how to correct its own mistakes," explains Karin. It does so by fooling the natural immune system into fighting itself by neutralizing the excessive cytokines and chemokines it is producing.
"Our laboratory has clearly shown that the major advantages of these self-generated antibodies lie not only in that they do not provoke an immune response, but also, and most importantly, in the ability they endow to the immune system to self-regulate their production in accordance with disease progression. This provides the immune system of a patient with an autoimmune disease with a powerful tool with which it can restrain its own harmful activities," says the Technion scientist.
Karin's laboratory has used the naked DNA technology to experimentally interfere with the inflammatory autoimmune process in the regulation of MS, and has recently demonstrated that chemokine-based DNA vaccines can be used to both treat and prevent rheumatoid arthritis. In the next stage, Karin continue exploring the vaccine using various vectors before testing it in humans.
Journal
Journal of Clinical Investigation