‘Magic Bullets’ Offer Hope in Multiple Sclerosis Cases

Using a technique developed through genetic engineering, a team of scientists from Stanford University, Columbia University and private industry has reversed a debilitating disease in mice that closely resembles multiple sclerosis. The results are so promising that the scientists hope to soon try the experimental treatment on human multiple sclerosis patients.

The treatment, if approved by Food and Drug Administration and the universities’ review boards, would consist of injecting patients with monoclonal antibodies, products of a new technology that enables researchers to produce unlimited amounts of an antibody with the capacity to attack any cell that the researchers wish to destroy.

These antibodies, also called “magic bullets” because of their ability to zero in on a specific target within the body, destroyed in the mice the type of cell believed to be responsible for the nerve damage that results in multiple sclerosis, Dr. Larry Steinman, assistant professor of neurology at Stanford University School of Medicine, said Thursday. Steinman is principal author of a report on the mouse experiments that will appear in the Jan. 25 issue of the journal Science.

Multiple sclerosis is believed to be an autoimmune disease, so called because it results from an attack by the immune system on a person’s own cells. When the disease strikes, certain cells in the immune system attack the sheathing that envelops nerves. The result is a life-long illness due to a deterioration of the nervous system. About 250,000 Americans are afflicted, and there is no good treatment.

In the animal studies, the researchers induced in mice a condition called experimental allergic encephalitis. In was used as the model because mice are not naturally afflicted with multiple sclerosis.

By injecting the mice in an early stage of experimental allergic encephalitis with the monoclonal antibodies, the researchers reported that within 72 hours they were able to arrest progression of the nerve damage in 90% of the animals.

In a separate study in which they gave the mice the monoclonal antibodies before inducing the disease, the researchers also reported that they prevented symptoms in all of the animals tested.

In the animal studies, the scientists used a monoclonal antibody that was directed against a protein located on the surface of a part of the immune system called a helper T-cell. The researchers have reason to believe the helper T-cell is the element of the immune system responsible for attacking and destroying the mouse’s nerve cells in experimental allergic encephalitis.

In a telephone interview, Steinman said his team believes that the same helper T-cell is the one that destroys the nerve sheathing in multiple sclerosis patients. The monoclonal antibody they propose to use on the human patients is the one that was successful in the mice.

“We have applied to the university human subjects committee and to the FDA, and when the approvals come through we will start,” Steinman said. He predicted that the human trials could begin in three or four months. However, Stanford said it may take as long as a year before such trials begin.

Steinman said the researchers’ biggest worry is that in destroying a patient’s helper T-cells, they may leave him or her vulnerable to a variety of infectious diseases that T-cells normally protect against. But, he said, no such side effect was seen in the mice, which were followed for about four months after treatment.

“If we give enough of the antibody it will destroy all the helper T-cells,” he said. “But we can adjust the dosage to achieve a balance that leaves some cells to protect against disease.”

Other scientists have warned that since the neurological disease suffered by the mice is not exactly the same as multiple sclerosis, patients with the human disease may not respond as well.

Although Steinman realizes that could be the case, he said he was encouraged because the protein on the helper T-cell in the mouse disease is identical to the one on the T-cells that characteristically infiltrate the brains of multiple sclerosis patients.

Another problem could result from the fact that the monoclonal antibodies that are commonly used on humans are derived from mouse cells. In the past, studies on humans using mouse-derived monoclonal antibodies have sometimes resulted in the patients rejecting them because of their foreign origin. When that happens, the effectiveness of the treatment is destroyed.

But Steinman said that another team of Stanford and Columbia researchers headed by Dr. Leonore Herzenberg, a Stanford geneticist, along with the Becton Dickinson Monoclonal Center Inc. in Mountain View, has developed a part-mouse, part-human monoclonal antibody against the helper T-cell protein. This antibody, called a chimeric antibody, is the one to be used on the multiple sclerosis patients.

Because of the human component, Steinman said, the chimeric antibody is not expected to be rejected. He added that he expects chimeric antibodies can be devised that would attack other kinds of proteins involved in causing other autoimmune diseases such as rheumatoid arthritis.