June 5, 2000

Summary: Mayo Clinic investigators, supported in part by the National MS Society, have reported success in promoting the regrowth of myelin in mice with MS-like disease:

• Mice with myelin damage caused by a virus were given injections of several different immune-system proteins called antibodies (in particular, monoclonal antibodies or pooled immunoglobulins) or inactive saline;
• Those that received certain monoclonal antibodies or immunoglobulins showed more signs of myelin repair in their spinal cords than those given saline;
• Additional preclinical research is ongoing in advance of possible clinical trials in humans with demyelinating conditions such as MS.

Details: Researchers led by Moses Rogriguez, MD, of the Mayo Clinic in Rochester, Minn., have reported success in promoting the regrowth of myelin (remyelination) in mice with a disease similar to multiple sclerosis. Results of the study, funded in part by the National MS Society, were published in the June 6 issue of the Proceedings of the National Academy of Sciences.

Background: Myelin is the wrapping that surrounds and insulates nerve fibers, and is the target of an immune-system attack in the brain and spinal cord in multiple sclerosis (MS). Its destruction leads to blocked or abnormal nerve signaling and a host of neurological symptoms. Although the body can repair some myelin damage, in MS this repair is insufficient.

Myelin is also targeted and destroyed by the immune system in an MS-like viral disease in mice caused by "Theiler's murine encephalomyelitis virus" (TMEV), which is the disease model used by the Mayo investigators to attempt remyelination.

If myelin could be repaired or regrown, especially where there is no underlying nerve damage, recovery of nerve function might occur, and with that, recovery of lost function might be possible. Current research focuses on several possible strategies for encouraging myelin repair: transplanting new myelin-making cells; harnessing natural "growth factors" to make myelin growth easier; and using internal "repair" capabilities of immune-system proteins called antibodies (in particular, monoclonal antibodies or pooled immuno-globulins). The latter approach is the one currently being tested by the Mayo investigators.

Previous studies by Dr. Rodriguez and colleagues had suggested the potential ability of pooled immunoglobulins, or IVIg, to stimulate myelin repair in animal models of MS. Several studies have also suggested a possible role of immunoglobulins in the treatment of MS and other immune-mediated neurological diseases. The Mayo group launched the current study based on the speculation that immunoglobulins were having an effect on myelin repair rather than simply altering immune-system activity.

The Study: The researchers identified human monoclonal antibodies, some of which target and attach to oligodendrocytes, the cells responsible for making and maintaining myelin. Mice infected with TMEV were given injections of one of several human monoclonal antibodies, or more general, pooled immunoglobulins (IVIg or IgM), or inactive saline solution (to serve as a control group). The mice given IgM, IVIg, or either of two human monoclonal antibodies had more areas of remyelination in their spinal cords than those given saline. Tests to determine whether the animals were clinically improved were not reported.

What the Study Means: Although no immediate new therapy or treatment will result from this study, the positive results indicating that immunoglobulins and human monoclonal antibodies can aid remyelination in animals with MS-like disease. This adds credence to the possibility that immune molecules such as monoclonal antibodies that target myelin-making cells may stimulate myelin repair in MS.

The Mayo group is conducting additional studies, with partial support from the National MS Society, to optimize the capabilities of these antibodies to stimulate myelin repair. In addition, Acorda Therapeutics, a biotechnology company that helped support this study, is proceeding with additional preclinical laboratory studies, including toxicity studies, prior to initiating human clinical trials for demyelinating conditions such as MS. It is not known how long the development of clinical trials will take or when they might begin.