MEDICINE : Some Strides in the Battle Against MS : Immunology: Experiments that defuse the body’s immune system show promise in treating and even preventing diseases like multiple sclerosis and diabetes.

A broad series of experiments suggest that it may be possible to defuse the immune system in humans to treat and even prevent diseases like multiple sclerosis and diabetes.

Researchers in Oregon and San Diego independently report they have used a synthetic molecule to immunize mice against an autoimmune disease--in which the body’s own immune system attacks its host--that is widely used as a model for multiple sclerosis. Clinical trials of the approach could be undertaken in humans within a year.

Moreover, researchers at Harvard are already using special antibodies in humans in an attempt to knock out MS patients’ own antibodies that are producing the disease. Stanford researchers are preparing to do the same.

The Harvard researchers are also vaccinating some MS patients with immune cells in an attempt to protect them from the ravages of the disease.

“There is a great excitement about extending these (animal) efforts to humans,” said neurologist Dale McFarland of the National Institutes of Health in Bethesda, Md. “We need things to get excited about. It’s good for the patients to know that there are a lot of people still trying.”

MS is a paralyzing neurological disease that affects as many as 250,000 people in the United States. It usually strikes in young adulthood and lasts for the remainder of the victim’s life, often 20 to 30 years. There is no effective treatment, although many patients go through long periods of spontaneous remission.

The disease occurs when the victim’s immune system goes awry and attacks the insulating protein sheath that surrounds nerve cells, effectively short-circuiting nerve impulses and producing the disease’s characteristic symptoms: weakness, tremors, disturbances of speech and vision, and ultimately paralysis.

In rodents and some other animals, an MS-like disease called experimental allergic encephalitis (EAE) can be produced by injecting the animals with ground-up nerve tissue. In an overreaction to the injected tissues, the animals’ immune systems begin to attack their own nerve tissues, producing MS symptoms.

The attack is carried out by immune cells, called T cells, that normally proliferate in response to an infection and destroy the foreign invader. In MS, some of the person’s immune cells inexplicably attack the nerve cells’ insulating sheaths.

MS researchers in the past have used drugs that wipe out all T cells in an attempt to halt the progression of MS, but such drugs leave the MS patient highly susceptible to life-threatening infections.

The goal of most research now is to deactivate only those specific T cells that are attacking the nerve sheath while leaving the rest of the immune system intact. The two major--and complementary--ways of doing this are called active and passive immunization.

In passive immunization, the researchers attack the T cells that have already been formed. If, for example, they know which specific type of T cell is attacking neural sheaths in EAE, the animal form of MS, they can produce special antibodies, called monoclonal antibodies, that bind to the T cells and help destroy them.

Several researchers have shown that monoclonal antibodies can slow and even reverse the progress of EAE, as well as diabetes, in mice and rats. Neurologist Howard L. Weiner and his colleagues at Harvard Medical School and Brigham and Women’s Hospital in Boston have used such antibodies to treat about 20 human MS patients.

In their safety trials, they have shown that the antibodies suppress the functioning of the T cells thought to be involved in MS, but they are not yet sure if they produced any remission of the disease because MS often goes into remission spontaneously.

Neurologist Lawrence Steinman of the Stanford University Medical Center is planning to begin similar trials soon.

In an active approach, such as that reported today in the journal Nature, the researchers hope to prevent the formation of the destructive T cells in the first place.

The foundation for this approach was laid by immunologist Irun Cohen of the Weizmann Institute of Science in Israel. For 10 years, Cohen has been isolating from rodents the T cells that cause EAE, diabetes and arthritis, treating them with radiation or chemicals to deactivate them so they do not cause harm, and injecting them back into the animals.

The immune system produced antibodies against the injected T cells--and thus against the identical T cells produced by the animals’ bodies. These antibodies hold the T cells in check and thereby block progression of the disease.

Weiner has already tried this approach in three human patients, isolating T cells from spinal fluid, deactivating them, and reinjecting them. As was the case with the monoclonal antibodies, the injections suppressed the undesired immune function, but Weiner has not yet been able to determine the clinical effects. Other researchers are expected to begin similar trials soon.

The results reported in Nature represent a more sophisticated way of achieving the same end. Neurologist Arthur A. Vandenbark and his colleagues at the Veterans Affairs Medical Center in Portland, Ore., synthesized a small chemical, called a peptide, that is a key part of the T cells that are involved in EAE.

When they vaccinated rats with the peptide, the rats no longer developed EAE when they were subsequently injected with ground nerve tissue. This approach is preferable to the use of whole cells because it is more widely applicable. In treating humans, the patient’s own deactivated cells must be used so that the injection does not cause an adverse immune reaction. But a peptide would not trigger such a reaction, and could be used to treat anyone.

Immunologists Stephen Brostoff and Marc Howell of Immune Response Corp. in San Diego said Wednesday they have achieved virtually identical results using a slightly different peptide. A report of their findings was presented at a recent meeting in England and will appear shortly in the journal Science.

Brostoff said his company hopes to begin trials in humans “within a year,” while Vandenbark predicted he would begin trials in “one or two years.”

BACKGROUND

Multiple sclerosis is a chronic neurological disease that causes weakness, tremors and paralysis in as many as 250,000 Americans. It results when the patient’s own immune system goes awry, and there is no effective therapy for it. Researchers have been attempting to halt its progression by interfering with the immune system activity that causes the disease.