Full Audio Visual Lecture at this URL:
15th May, 2002
Summary - not a transcription - see above URL for full lecture
Scientists respond to the challenge of multiple sclerosis
Should people with multiple sclerosis (MS) suppress their immune system in the early stages of their disease in an effort to save their nerves as they get older? This is the question that a growing number of young people with the disease are likely to face as new generations of powerful immunosuppressant drugs go on trial.
During the May Science Today, Health Tomorrow lecture at the Royal Institution, Cambridge University scientist, Dr Alasdair Coles, described the fascinating research which is slowly uncovering the reasons why immune cells attack the nervous system in MS, leading to movement and other health problems. But there may be a price to pay if researchers find out how to disable people’s immune systems in an effort to save their nerves.
‘By using powerful immunosuppressant drugs to target the immune cells that are involved in MS, we may be laying people open to infection and other diseases. In effect, we are asking people to take drugs with serious side effects when they are well in the hope that we are protecting their nerves for the future,’ explained Dr Coles.
With 85,000 people affected by the disease in the UK, MS presents a significant challenge to doctors and scientists. But advances in scanner technology, especially magnetic resonance imaging (MRI), have meant that they can now watch and monitor the changes in the brain and spinal cord that lead to nerve damage and muscle weakness in people with MS.
‘With these powerful tools, we are starting to see what effects our treatments are having and we are also seeing just what a complicated disease MS really is,’ explained Professor Alan Thompson, head of clinical neurology and neurorehabilitation at the Institute of Neurology, London.
He showed the patches of inflammation that are visible on brain scans of people with MS which mean that immune cells are attacking the protective myelin coating which surrounds nerves in the brain and spinal cord. Like spots on the skin, these inflamed and swollen areas come and go over four to six weeks. Sometimes they cause lasting nerve damage, sometimes they don’t.
Depending on which areas are inflamed, people may get movement impairment
or other symptoms and, if there is lasting damage and nerves are destroyed,
their MS is likely to progress. Current immunosuppressive drugs, such as
beta interferon and glatiramer acetate, damp down inflammation and reduce
relapses in MS, and they may also help to slow disability. But most people
with MS need physio- and other therapies to keep them as mobile as possible
and minimise disability.
‘We are making progress but we need to set up standards of care from diagnosis to disability which will encourage better management of MS,’ Professor Thompson concluded.
At Cambridge, Dr Coles is trying to find out whether disability in MS is the end result of the patches of inflammation in the brain and spinal cord which are seen at an early stage of the disease or of some other process. Recent studies of new, more powerful immunosuppressant drugs, such as the antibody treatment, CAMPATH 1H, have shown that damping down inflammation may reduce relapses in MS but it doesn’t necessarily prevent progressive disability. It seems that those who become increasingly disabled despite the anti-inflammatory effects of the antibody have already lost a lot of nerve fibres. Their brains have shrunk and become smaller than those who do not have progressive disability.
Laboratory studies suggest that this may occur because the brain cells, called oligodendrocytes, which produce protective myelin also make nutrients that nerves need to grow and function normally. When inflammation damages the oligodendrocytes, it is not only affecting myelin production it is also cutting off some of the brain’s food supply.
‘One way to prevent this would be to get in very early in the illness and give powerful immunosuppressant drugs not only to reduce the inflammation and demyelination but also to prevent the later consequences of nerve deterioration arising from the nutritional deficiency,’ Dr Coles explained.
But, by destroying immune cells with this early immunosuppression, treatment could leave people open to serious viral infection – much like people with poor immunity as a result of AIDS. Preliminary results suggest that viral infection is less common than might be expected when people with early MS are given immunosuppressant drugs, but a lot of research is still needed to show whether the benefits to the brain and nervous system outweigh the risks of infection.
In the meantime, researchers are looking at alternative ways of saving the nerves of people with MS. They are trying to grow cells in the laboratory to replace the damaged oligodendrocytes and they are testing natural substances, such as insulin-like growth factor (IGF-1), to see if they can repair nerves after they have lost their protective myelin coating.
As Dr Coles told the audience, scientists have some promising leads in the fight against MS but, as with so much medical research, they will need some committed volunteers for trials of new treatments who will accept the risks without expecting immediate cures: ‘It’s critical that we go backwards and forwards between the laboratory and the clinic, applying the knowledge that we gain from each of them, to further advances in our understanding and treatment of MS.’
1. What is the reason for the sharp geographical variations in the incidence of MS between equatorial regions and high latitudes?
The most likely explanation is that it is due to a combination of unidentified environmental agents and a genetic component. We know that different populations have different genetics, for example, the genetics of equatorial Africa are different to those of Scotland. The environmental agents that trigger MS will therefore have different impacts on these populations. This is demonstrated in genetic archaeology where you can see that the genetics of people living before the Plague were very different to those living after. The Plague killed a whole sector of our community with a particular genetic background but left others unaffected.
2. What causes fatigue in MS and what role does Provigil have?
There are a number of different elements to fatigue - some people have fatigue at the time of an attack and others have constant fatigue. But some of this fatigue can be due to a general lack of respiratory fitness due to ill health rather than the disease itself.
Provigil is mainly used to treat narcolepsy but it is now licensed in the US for the treatment of fatigue. It seems to work for a proportion of patients and is well tolerated. It has been used more in this country in the last two months or so and I expect we will hear more about it.
3. Could you explain whether the use of powerful immunosuppressant drugs affects the ability to fight off other infections?
These immunosuppressant drugs do affect the body's ability to fight off other infection, and this is the great difficulty with the treatment. The ideal drug would be the one that targets the components of the immune system that are responsible for the disease and no other, leaving the rest of the system competent to deal with infection. But at the moment we have to target just a part of the immune system where the problem lies and the more powerful the drug, the more widely that person is laid open to infection.
4. Is Crohn's disease a side effect of MS?
A link between MS and other inflammatory conditions is often speculated about but up until now, there has been little compelling evidence to show a link. However, a study at Cambridge has shown that patients with MS have a slightly increased risk of developing other autoimmune diseases. Thyroid disease was the most common other disease seen in this study.
5. Do you have any comments on the use of bee venom in MS?
Bee venom is a very potent agent in producing an immune response. It is early days to consider this as a real therapy because the immune system is so complex.
6. What is Campath - 1H and how does it work?
Campath - 1H is an antibody made in Cambridge designed to latch onto and kill the T-cells, the white blood cell that protect the body against viral infection. Campath -1H knocks out the T-cells dramatically and profoundly, so much so that they do not return to normal for up to six years. There is concern about the impact this has on the patient and exposure to other viral infections but the number occurring in patients taking Campath so far has been quite low.
7. What research initiatives are being undertaken in the gender difference in MS?
There are studies ongoing in the US to look at the differences in incidence between males and females and more particularly, the hormonal influences on MS.
8. Is MS hereditary?
In the true sense of the word where the disease is passed relentlessly from one generation to the next like in Huntington's chorea, then no, MS is not hereditary.
However, it does have a minor inherited component. If your parents have MS, your risk of developing it increases from the 0.2 percent risk of the general population to 2 percent. But there are families who have an increased number of family members affected but at the moment we cannot distinguish whether there is something special happening here or whether that family is just unlucky.
9. Is it practical to instigate a monitoring programme in the families with MS to catch people at an earlier stage of the disease?
We have diagnostic clinics were people can get access and be diagnosed more quickly but they are in a limited number of centres. We would like to see more of these so that we can pick MS up earlier and get treatment started earlier but they need to be supported by all the relevant services.
This is one of the key themes of the National Service Framework for Neurological Disability. Also, the NICE guidelines for the management of MS should focus on this as well.
10. How can people put themselves forward for Campath-1H?
They need to see their GP or contact the Multiple Sclerosis Trust.
11. Is pregnancy contra-indicated in MS?
Twenty years ago the answer to that question would have been yes. However, we know more about pregnancy in MS now. We know that pregnancy will have an effect on the condition - a combination of an improvement during the pregnancy with a slight worsening after the birth. Therefore, the issues do not relate to the condition itself but to other aspects of having such a disease. It would be a problem if she was to take immunospurrpressant therapy though and treatment would have to stop during pregnancy and then resume afterwards.