TEACHING TOLERANCE
New vaccine holds promise for chronic multiple
sclerosis.
by Eva
Emerson
When Leslie Weiner, M.D., talks about tolerance, his reference is purely physical. Weiner is referring to the immune system's process of purposely ignoring, or "tolerating", the body's own cells. But sometimes in autoimmune diseases, the immune system becomes mysteriously intolerant.
In the case of multiple sclerosis (MS), Weiner's specialty, the body mounts an immune attack against its own myelin protein that forms a protective sheath around the body's nerve fibers. Eventually, this immune intolerance may injure the nerves and lead to the disabling symptoms of multiple sclerosis.
The goal of his small, ongoing clinical trial is to fight MS by retraining retrain the immune system so it will once again tolerate the body's own myelin. With promising results in hand, Weiner hopes to expand the trial to learn if the novel therapy can help those who have no other option.
In some people, the disease may wax and wane, bringing unpredictable symptoms of numbness, loss of mobility and vision problems. In the last decade, effective drugs have become available for people with the relapsing-remitting form of the disease. Before these drugs became available, about half of people with relapsing-remitting MS would have their symptoms worsen and go on to develop chronic disease. It is these patients whom Weiner hopes to help with his new treatment.
His plan is to use what he calls a vaccine to train the immune system to kill the pathologic or bad immune cells that have become intolerant and do damage.
Weiner and his colleagues tried the vaccine in four patients with advanced MS. Now, two years later, three patients have stabilized and one has had some progression.
To make the vaccine, the researchers collected blood from each patient and selected out the immune cells, called T-cells, which attack myelin. Each patient's myelin-reactive T-cells were then grown in the laboratory until they numbered about 400 million. For each treatment, researchers took a portion of the cells and killed them using a high dose of radiation. Each patient received a monthly vaccine of their own inactivated myelin-reactive T-cells for several months and then quarterly over two years.
In his preliminary study, Weiner found that the influx of a huge number of inactivated bad T-cells triggered an immune. This immune response selectively targeted any live anti-myelin T-cells still in the blood and brain.
"Basically, you retrain the immune system to recognize and rid the body of its traitorous myelin-reactive T-cells," Weiner says. Physicians do this by injecting large quantities of dead myelin-reactive T-cells, which stimulate a favorable response from the immune system.
The results look good. After regular treatments with the vaccine over two years, the four patients had undetectable levels of these traitorous T-cells.
Researchers also found lower levels of immune proteins that damage nerves directly and signal the body to make more myelin-reactive T-cells following the therapy. Using magnetic resonance imaging, the team scanned the brains of patients, showing that one patient had fewer lesions, two were stable and one had developed a single additional lesion by the end of the study.
"Three of them, at least, are not getting any worse. And they were getting worse before treatment," Weiner says. "It appears that we are doing something useful, even dramatic." Weiner has submitted a proposal to expand the study to 80 patients.
Besides improving care for patients who currently have few options, the study holds great scientific interest, Weiner says. By determining whether getting rid of reactive T-cells stops the progression of MS, Weiner is also testing a long-held hypothesis that reaction to myelin proteins is responsible for MS.