RESEARCHERS have long believed that multiple sclerosis (MS) is an “autoimmune” disease, caused by the immune system attacking nerves and stripping them of their fatty wrappings. Without these wrappings, known as myelin sheaths, electrical impulses cannot travel along nerve fibres. This leads to the deterioration of mind and body which is symptomatic of MS. However, a study published in the Annals of Neurology by John Prineas and Michael Barnett, of the University of Sydney, suggests that the immune system may not be to blame, after all. Instead, these researchers think that the myelin sheaths are destroying themselves.

Studying the cause of MS is difficult. Most patients have a form of the disease that comes and goes irregularly. Because such patients usually recover from their relapses, it is hard to look at what is going on in their nervous systems in order to find out what causes the symptoms. Instead, researchers are left with the aftermath—myelin sheaths that have been invaded by T-cells and macrophages from the immune system. The assumption has been that these immune cells cause the disease. But correlation is not the same as proof.

Some people, however, die during or shortly after a relapse. Dr Prineas and Dr Barnett reasoned that in these cases the causative factors would be “frozen” in the patients' nervous systems, and could be discovered during autopsies.

To test this idea they studied the corpses of 12 patients who had died in relapse. They found that all 12 had the scars typical of MS in their nervous systems. What was unexpected was that the patients' myelin sheaths were largely intact, and showed little inflammation. In particular, there was no sign of the “killer” T-cells of the immune system that were assumed to be causing the problem, nor of the macrophages that clear up the mess that T-cells create.

In seven of the 12 cases, however, oligodendrocytes—the cells that actually make myelin—were surrounded by microglia, another type of cell found in the nervous system. The role of microglia, like that of macrophages, is to clean up the debris of dead and dying cells. In the case of Dr Prineas's and Dr Barnett's patients the microglia had engulfed and chewed up the oligodendrocytes. Once the oligodendrocytes are dead, Dr Prineas and Dr Barnett reason, the sections of myelin sheath they support will disintegrate.

Microglia do not, however, normally kill other cells. So something else must be happening. The researchers suggest it is a process called apoptosis. This is a fancy name for cellular suicide.

Cells often kill themselves for good reason. If a cell “realises” that it is infected with a virus, or is part of a tumour, suicide is a sensible option. Apoptosis is also common during embryonic development, when removing superfluous tissue is as important as growing necessary new tissue. Apoptosis should not, however, occur in healthy cells. Nor should it attract the attention of the immune system. Dr Prineas and Dr Barnett suspect that the immune system gets involved in the case of MS because myelin sheaths are so large that their disintegration overwhelms the local clean-up mechanisms such as microglia. Enough myelin is thus left over to trigger an immune response. But what causes the apoptosis of oligodendrocytes in the first place is still as much of a mystery as it is a tongue-twister.