Progress Reported in Battle Against MS : Medicine: Caltech researchers say a new technique is extremely effective in treating and preventing a form of multiple sclerosis in mice.
Caltech researchers reported Thursday that they have significantly improved an experimental technique for treating and preventing a multiple sclerosis-like disease in mice.
Their new approach cures a larger percentage of mice--as many as 95%, compared with the 70% in previous attempts. It also has the advantage, if the results can eventually be extended to humans, of specifically attacking the immune system cells that cause the disease without significantly impairing the body’s ability to fight off infections.
“This takes us one step further” in developing potential therapies for MS, said Dr. Howard L. Weiner of Brigham and Women’s Hospital in Boston, one of the leaders in previous attempts to use similar therapy in humans.
MS is a so-called autoimmune disease in which the body’s immune system attacks its own cells, specifically the myelin sheaths that encase nerves. The loss of the nerve covering, in effect, short-circuits the nerve paths, interfering with sensation and control of movements. Victims may suffer weakness and numbness, difficulty walking, visual impairment, slurred speech and other symptoms.
The disease affects as many as 150,000 Americans, and its course is variable. Some people may have one attack and then return to a normal life. Others may have multiple attacks that cause severe degeneration. In the worst cases, the disease produces complete disability.
An analog of MS, called experimental allergic encephalomyelitis (EAE), can be produced in mice by grinding up myelin nerve coating and injecting it. The mouse’s immune system produces antibodies against the injected coating, and these antibodies attack its own myelin sheaths, producing the disease.
The specific component of the immune system that attacks the myelin sheath is called helper T-cells. Several researchers showed in the early 1980s that specialized, laboratory-produced antibodies called monoclonal antibodies would react with the T-cells and destroy them, thereby preventing EAE from developing, or reversing it once it starts.
Versions of these antibodies produced in mice were actually used to treat human MS patients in 1987. They produced modest improvements in the patients’ conditions, but the patients’ bodies suffered an allergic response to the mouse antibodies and their use was discontinued.
Even if the therapy had worked, furthermore, the wide-scale destruction of all helper T-cells would have left the patients susceptible to other diseases. Researchers have thus been attempting to find more specific antibodies that would interfere only with the attack on myelin. That is where Caltech molecular biologist Leroy E. Hood has made an advance.
Hood and others had previously produced monoclonal antibodies against one specific type of helper T-cell that attacks myelin and found that they could cure about 70% of mice--good, but not adequate for effective therapy.
Now, Hood and his colleagues have found that the efficacy can be improved to 95% by adding a second monoclonal that attacks another specific helper T-cell. With the two antibodies, said Hood’s colleague, molecular immunologist Dennis Zaller, “only one of 20 animals got the disease, and that case was rather mild.”
That success is promising, but Hood and Zaller caution that the results will not be applied to humans soon. “In my opinion, our technique is at least 10 years away from human application,” Hood said.
The most important problem that the potential new therapy faces is that the monoclonal antibodies, like those previously used in human trials, are made from mouse cells. Humans would thus be expected to develop an allergic reaction to the antibodies, which would be a particular problem because the therapy would probably have to be repeated at regular intervals.
An even more fundamental problem is that researchers have not yet identified the human counterparts of the disease-causing helper-T cells in mice. To be really effective, the monoclonal antibodies would have to be directed specifically at those human receptors.
“There are potential ways around these problems,” Zaller said, but finding them is going to take some time.