The causes of multiple sclerosis (MS) are still unknown. Although it is common, with at least 80,000 cases in Britain alone, there is, as yet, no cure. MS is an autoimmune disease affecting the nervous system. The development of the disease and the symptoms are highly variable. In some people, it appears suddenly and progresses rapidly. In others, it can be so mild that it passes unnoticed. In many cases, the symptoms may disappear as mysteriously as they arrive. For the unfortunate, it is completely debilitating and can be fatal. About 25% of cases are steadily progressive with the remainder characterized by unpredictable ups and downs. It is thought to have a genetic component, but this has not been proven.
The disease affects otherwise healthy individuals, usually young adults, with multiple lesions of the central nervous system. These lesions result in problems with co-ordination, slurred speech (dysarthria), numbness, paralysis, urinary incontinence and blindness. Sufferers often do not know which part of the body it will attack next.
Although humankind have made great advances in many areas, they have made little progress in understanding the brain and its operations. The starting point for understanding multiple sclerosis or any other neurological illness is an examination of the smallest unit of the brain, namely the nerve cell or neuron. The neuron is made up of a cell body (called a soma) and one or more long processes - a single axon and dendrites. The structure resembles tree trunks growing from a frizzle of roots (see diagram).
The roots, called dendrites, serve mainly to receive incoming messages from other neurons. The trunks, known as axons, transmit the messages and are covered with fatty insulating sheaths. These myelin sheaths are the focus of research into MS. The myelin contains a protein referred to as myelin base protein (MBP). Deterioration of this myelin sheath, particularly the MBP, is characteristic of multiple sclerosis. The myelin ensures that the electro-chemical charges communicated by the neurons are transmitted efficiently. If the sheath is damaged, signals 'leak out' causing the slurred speech, numbness, etc., associated with MS.
There are several approaches to dealing with MS. We can try to understand why the sheath becomes damaged in order to work out how to repair it. We can experiment with animals (typically rats), in whom MS-like symptoms have been induced, and search for a vaccine. Also, we can look to the body's own healing system and try to understand why (for example) children do not normally get MS and whether the body can reverse the process 'naturally'.
Whatever approach we take, we will never find a permanent cure unless we understand the complexities of the brain. So far, we have come nowhere near even a partial understanding of this marvel of creation. Fortunately, understanding all of creation is not a pre-requisite of searching for a cure.
One approach, as we noted, concentrates on finding ways of repairing the myelin sheath. This idea would have been unthinkable even a few years ago. However, in 1993, Charles French-Constant, at the Centre for Brain Research, identified re-myelination, that is, a reversal of the process, in newly formed lesions of sufferers experiencing the early stages of the disease. It appears that the body tries to regenerate itself but, with most MS sufferers, it is unable to do so fully. The basis of French-Constant's research is that this regeneration might be enhanced if a chemical trigger could he found to improve the limited capacity for healing. His work starts by looking at the natural healing processes. Repairing even only 5% of the damaged nerve fibres would bring considerable relief to a large percentage of MS sufferers. For example, it could eliminate most bladder malfunctions related to MS. In effect, the disease would appear to he 'contained'.
Humans are born with all the brain and nerve cells they are likely to need during their lifetimes. Throughout the life of living organisms, nerve cells die. If the cells which lead to the sheathing of the nerve cells could be found in an inactivated state in MS sufferers, and then encouraged to migrate, proliferate and repair the damage caused by the degeneration of the myelin, the processes of remyelination could be encouraged. The body would heal itself.
Research to identify the origin of the cells which end up insulating the axons began in the l98Os on rats. This work with rats suggests that these cells may still be present in fully developed adults, However, optimism must be cautious. As with other experiments, early results with cats have shown that scaling-up results is not always straightforward.
Even if the right cells can be found in the body, creating the correct chemical environment for regeneration is still going to be difficult. Another problem is that even if remyelination can be encouraged, this does not necessarily mean that de-myelination has been halted. The disease has to he attacked from both directions.
The new 'vaccine' about to be tried in America was developed by David Topham of St Jude's Hospital in Memphis, Tennessee. Instead of trying to support the regeneration of the myelin, he attempts to stop the process that attacks the myelin sheath.
The body's immune system, primarily in the form of T cells, naturally attacks antigens from viruses and bacteria which are seen as foreign organisms. In multiple sclerosis, the protein of the myelin sheath (MBP) is mistakenly attacked in the same way as an antigen might be.
In the early l980s, researchers found that they could reduce the number of cells which attack the myelin in a MS type illness in rats by inoculating them with inactivated T cells. In 1993, Jingwa Zhang managed to demonstrate a similar pattern in six humans using their own weakened auto- reactive T cells (Science, 261, p.145l). This was based on 'naturally occurring cells'.
Bill Blackmore, at the Cambridge Centre for Brain Research, has been attempting to culture cells from donors. Others at the Centre have taken cells from patients in the early stages of re-myelination, cultured them in a laboratory and, after a severe attack, reintroduced them along with the necessary growth factor into the damaged area. This has the advantage that rejection is less likely.
A more controversial approach uses post-natal tissue. Cultured fetal tissue has been used in Sweden and America in an attempt to treat Parkinson's disease. But this procedure raises a number of serious ethical questions.
Any significant breakthrough in the treatment of MS is likely to have implications for the treatment of arthritis. This is what is hoped for with the latest attempt to find a cure. Earlier this year, 300 Americans suffering from severe rheumatoid arthritis were treated with a drug which aimed to 're-educate' the T cells. It was hoped that this would result in them protecting the relevant cells rather than destroying them. The manufacturers claimed that four people were completely cured of the illness. The results were encouraging. A peptide produced by Topham, the developer of the latest vaccine, has already been used on joint tissue by other research groups.
These attempts to 'cure' MS may produce results, but all the researchers will admit that the central problem is lack of knowledge about how the brain operates. Much of the nervous system is still a complete mystery. The search for a cure will continue to go on. There is a cure and we have to search for it, for we have been assured that 'for every illness there is a cure'.