WESTPORT, Jun 06 (Reuters Health) - Human monoclonal antibodies (mAbs) against oligodendrocyte proteins promote significant remyelination in a mouse model of multiple sclerosis, researchers report in the June 6th issue of the Proceedings of the National Academy of Sciences.
Dr. Moses Rodriguez of the Mayo Clinic in Rochester, Minnesota, and colleagues there and in France and Japan infected mice with a virus that leads to a multiple sclerosis-like disease.
They then treated the mice with one of six human mAbs that had been shown to bind to rat oligodendrocytes and found that two of them promoted significant levels of remyelination over background. Many of the antibody-treated animals had at least one area of completely repaired white matter.
In comparing the effectiveness of the human mAbs with human polyclonal antibodies or human intravenous immunoglobulin, the researchers found that the mAbs were significantly better than intravenous immunoglobulin but were similar to polyclonal human antibodies.
Of the six human monoclonal antibodies tested, three bound to human oligodendrocytes, including the two that were effective in promoting remyelination in the mice. In contrast, neither human polyclonal antibodies nor intravenous immunoglobulin bound to human oligodendrocytes.
"An affinity for oligodendrocyte antigens may be necessary, but is not sufficient for a human mAb to promote remyelination," Dr. Rodriguez and colleagues write. They add that "alternatively, targeting human mAbs to areas of central nervous system pathology may facilitate the opsonization of myelin debris, allowing repair to proceed."
"In contrast to mouse mAbs or 'humanized' mouse mAbs, human mAbs should result in minimal immune response and are readily applicable to human trials," the authors continue. "Given that human mAbs promoted remyelination in chronically paralyzed animals provides hope that successful therapies can be developed for patients with long-standing disabilities."
Proc Natl Acad Sci USA 2000;97:6820-6825.