Damaged myelin can be repaired with the use of human monoclonal antibodies. A team of immunologists led by Dr Moses Rodriguez at the Mayo Clinic in Minnesota has discovered two human monoclonal antibodies that seem to promote the repair of damaged myelin (Proceedings of the National Academy of Sciences 2000;97:6820-5).
The idea that antibodies may be useful in myelin repair came from observations made about 10 years ago. Dr Rodriguez discovered that mice immunised with a spinal cord homogenate (containing myelin) produced a serum which, when put into demyelinated mice, seemed to promote repair of their damaged myelin.
This suggested to Dr Rodriguez that the antibodies induced by this particular immunisation process were responsible for promoting myelin repair.
In this latest study, Dr Rodriguez's team obtained 150 different monoclonal antibodies from patients with monoclonal gammopathies and other blood dyscrasias and screened them for action against human oligodendrocytes (the central nervous system support cells which are damaged in demyelinating diseases) in vitro. The researchers identified six antibodies which bound to these oligodendrocytes, and, of these, two were significantly associated with myelin repair.
One theory to explain this is known as the “scavenger hypothesis.” The antibodies bind to damaged oligodendrocytes, and the debris which is created by these antigen-antibody complexes is then removed by macrophages, allowing spontaneous repair.
Such spontaneous repair is usually inhibited in multiple sclerosis and other demyelinating diseases, presumably by the presence of the damaged cells.
Dr Rodriguez's team was able to sequence one of the two active monoclonal antibodies and so theoretically could manufacture large quantities of it. The researchers had an insufficient amount of the second antibody to sequence it fully, and they were unable to obtain a larger sample because the patient has since disappeared.
Their next step will be to test the manufactured monoclonal antibody against many different animal models of multiple sclerosis. If its efficacy is confirmed and the risk of toxicity is acceptable, they will be going on to test it in clinical trials.