Responding to the Reader
Multiple Sclerosis
Story by Tara Narwani/Illustration by Carolyn Fisher
A reader asks about new research on MS.
About this feature
AHFMR frequently receives letters requesting information about Heritage research or about various medical conditions. "Responding to the reader" is a Research News feature intended to provide up-to-date information related to readers' questions, with the help of experts in the Alberta research community. AHFMR cannot provide medical advice, however; please consult your family physician about your specific health concerns.
The task of the human immune system is to protect the body from foreign organisms and substances. When the system breaks down, immune cells can attack and damage the body's own tissues, causing autoimmune diseases such as multiple sclerosis (MS). We asked Dr. Hanne Ostergaard, an AHFMR Scientist working in immunology at the University of Alberta, why research in MS has focused on T cells of the immune system, and whether recent work with another type of cell, the B cell, holds any promise for MS patients.
"Multiple sclerosis is a disease where the immune system attacks the central nervous system (CNS)," Dr. Ostergaard explained. Nerve cells of the brain and spinal cord form a network by means of which the CNS and the rest of the body communicate. The cable-like extensions of the nerve cells, called axons, have a protective covering made out of myelin that transmits signals efficiently.
In MS, the body's own immune system damages the myelin, interrupting the electrical impulses that travel along axons. The result is the range of symptoms associated with MS, including loss of muscle control, vision problems, and difficulty with balance.
To treat—and ultimately cure—MS, researchers have to identify the parts of the immune system that go haywire and start destroying nerve cells. This is no easy task because so many different types of cells are involved.
Two cell types are essential to a functioning immune system: T cells and B cells. Both work at detecting foreign substances (antigens) in the body. But once they recognize the antigens—such as bacteria, viruses, toxins, and even transplanted tissues—T cells and B cells initiate quite different immune responses.
Over the years, researchers have thought that B cells played a limited role in the immune system: recognizing antigens, then producing antibodies to neutralize them. By contrast, they have regarded T cells as the more important players, because of two things they do: they kill infected cells and they help B cells make antibodies. In other words, because T cells can regulate other immune responses.
To determine whether T cells or B cells cause MS, researchers have used a model called EAE (which stands for Experimental Autoimmune Encephalomyelitis) to represent MS development in humans. Ethical considerations prevent direct experimentation on humans.
"People focused on T cells in MS because you want to treat the cell you think causes the disease. By transferring T cells from an EAE model to a healthy model, you can trigger MS in the healthy model. That suggested T cells cause MS," says Dr. Ostergaard. Since parallel experiments with antibodies from B cells didn't induce the disease, subsequent research attention was directed almost exclusively at the role of T cells in MS.
With the advent of new genetic tools, though, more experiments with B cells have become possible. Results show that B cells may do different things during the early and later stages of MS. "In the triggering stage, B cells may be protective; whereas, at the disease-progression stage, they may actually contribute to the disease," Dr. Ostergaard says, adding that we don't yet know whether B cells play the protective role in humans. However, the apparent dual action raises the idea that B cells might do more than secrete antibodies. They're now viewed, along with T cells, as possible regulatory cells.
Conclusions drawn from new experiments suggest that reducing B cells in humans could halt the progression of MS. In fact, a Phase II clinical trial for the drug rituxamab (already approved for use in non-Hodgkin's lymphoma) was recently completed with MS patients as subjects. It came into being because that drug had been observed to reduce levels of B cells. The results of the trial showed reduced number of lesions in the central nervous system of MS patients who had taken the drug. This is a key indicator of the progression of the disease. Also, more than half of the patients saw a reduction in the recurrence of their disease symptoms over 24 weeks.
A Phase III clinical trial for rituxamab in MS patients has now been approved, to look at the long-term effects of the drug. Dr. Ostergaard is optimistic, but cautious. "You could make a person so immunocompromised that they don't have MS, but they might not survive a simple infection. Those are the kinds of things they'll be looking at in Phase III."