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.
More
information is available about this study on the Mayo Clinic's website (www.mayohealth.org)
and on Acorda Therapeutic's website (www.acorda.com).