Genetic research

Chapter 1 discusses the possible causal relationship between MS, genetics and the environment. The most striking thing now is the speed at which research on possible underlying genetic factors is being undertaken. Of course, this research is part of the massive international research effort which has now ‘mapped’ human genetic makeup – in other words which has unravelled the human ‘genome’. In the course of this research more and more genetic associations with particular diseases are being uncovered. Of particular interest is the fact that genes control the human immune system, and so, if it turns out that people with MS have a clearly different genetic makeup to other people, ultimately the most effective way to manage immune system malfunctions may be to try and deal with those genetic differences. This will not be a simple process because several genes are already known to be implicated in MS, unlike some other conditions where only one gene is involved.
Currently genetic research on MS is based on two main lines of inquiry:

• Genes that allow the body to recognize which are its own tissues and which are those of an ‘invader’ bacteria or virus are being studied. If this recognition process goes wrong, then an
‘autoimmune’ attack of the body’s own tissue is likely to occur, as in MS. The genes under investigation here that perform this recognition function – ‘histocompatibility genes’ – are usually either HLA (human leukocyte antigen) genes, or MHC (major histocompatibility) genes.
• The genetic control of ‘lymphocytes’ (T cells), which are one important class of cells responding to insults to the immune system, is the second line of study. Although there is much detailed research still to be undertaken, it appears likely that a combination of genes controlling these lymphocytes and related immune
activity produces a susceptibility in people with MS to the disease, although other triggering factors, perhaps environmentally determined, may be necessary for the onset of the disease.

Research on viruses and Multiple Sclerosis

The relationship of viruses to MS has been the subject of much research over the past two decades, and causes an equal amount of controversy. Almost every year, it has been claimed that a virus specific to the cause of MS has been discovered. However, none of these claims has been sustained after further extensive investigation. The basic issue is really one of cause or ef fect. Does a virus cause Multiple Sclerosis, or does a weakened immune system have the effect of making the body more susceptible to attack by viruses? Most researchers believe the latter to be the case, but an existing faulty recognition process in the immune system may either also fail to recognize (and thus attack) an invading virus, or such a virus may, through the same process, accelerate the body’s own attack on itself. In this respect recent work on viruses is being linked to other research on malfunctioning immune systems, and genetic research is also continuing.

Regeneration of myelin

This research area – trying to regenerate myelin – has been significant over the past few years. The cells that produce myelin are called
‘oligodendrocytes’, one of a family of what are described as ‘glial cells’. If the life of oligodendrocytes could be fully understood, as well as their role in the formation and repair of myelin, then an attempt to encourage their revitalization in MS could be made. This research process has also involved investigating exactly how the nervous system responds to myelin damage and how scar tissue is formed, as well as estimating what effects regeneration of myelin might have.
Research on myelin damage and possible regeneration is yet another story of an initially hopeful scientific development followed by major disappointment. For some time it was thought that myelin could not be regenerated at all, and then more sophisticated techniques indicated that myelin repair did occur in Multiple Sclerosis, although it was very slow and weak – and was not enough to compensate for the original damage. Now scientists are concentrating on seeing whether and how this process of repair might be made more effective. The importance of this research is the knowledge that, even if myelin has been lost (and thus messages along the nerves are malfunctioning), the underlying nervous tissue is almost certainly still intact, at least in the early stages of MS; thus, if it was reinsulated (remyelinated), it may well be able to function normally. Once demyelination has occurred for some time this may be less likely.
Animal models have suggested that remyelination is possible in such a way as to restore some functions originally lost. Strategies have included:

• using substances called growth factors to enhance the actions of myelin-producing cells;
• trying to inhibit other processes that weaken the actions of those cells, or
• in a more adventurous way, investigating the possibility of transplanting cells to produce myelin.

There are a number of substances being tested on humans to assist remyelination, although the lessons of the disappointments of equally promising possibilities arising from animal work with EAE (see above) are important to bear in mind. It is also important to say that most of the remyelinating strategies are essentially compensatory ones, i.e. they do not address the underlying disease process that is still going on – whilst some remyelination may be assisted, other demyelination may be occurring or about to occur. In addition for those with long-standing Multiple Sclerosis, the underlying nervous tissue will probably have been damaged, as well as the myelin coating of that tissue. In such a situation, remyelination may have little or no effect on symptoms.