Science Interviews

Interview

Sun, 9th Nov 2008

Multiple Sclerosis: Successful Treatment

Alistair Coles, University of Cambridge

Listen Now    Download as mp3 from the show National Pathology Week

Alistair - If you see a young adult in this country that is disabled then the likely thing is that they have multiple sclerosis. This is the commonest disease of the brain and the spinal cord amongst Caucasian people in the west. It’s a disease where the immune system attacks a particular part of the nerve in the brain or in the spinal cord. That particular part is the myelin sheath. What that means is the insulation that covers the nerve. This means that nerves can lie across each other and short circuit or impulses intended for one area can cross over to another nerve and not reach their target. You get electrical confusion in the brain.

Chris - Does this happen everywhere or is it quite discrete bits in the brain that get affected?

MS MRIAlistair - You’re quite right. The immune attack is just on specific patches within the brain. Each patch will go through a period where there is lots of inflammation. It may cause symptoms but then it resolves and dies away to leave some scarring only for other areas of the brain to become involved.

Chris - Do you know what bits of the immune system are doing that damage?

Alistair - Multiple Sclerosis is one of these diseases where we are all capable of getting it. If I looked in your blood, or in my blood or anyone else’s blood we would find cells of the immune system: T-lymphocytes that are aggressive towards myelin, towards the brain. The thing that’s stopping you or I from getting Multiple Sclerosis is that we have another set of cells called the regulatory T-cells which prevent the aggressive T-cells from carrying out their attack. In people who have Multiple Sclerosis the defect is that their regulatory T-cells are not working properly.

Chris - So what have you been looking at in terms of how to get people to have the best outcome possible for them?

Photomicrograph of a demyelinating MS-Lesion.Alistair - Our initial logic was very simple. It is to say MS is a disease where the immune system attacks the brain. Let’s disable the immune system and it will no longer attack the brain. We looked around for a drug that might do that and we came across alemtuzumab, or as it was known then CamPath. We said that this is a drug that deliberately hones in, identifies and kills one of the cells of the immune system: the lymphocyte. It disables the immune system very effectively.

Chirs - What was the nature of that trial? How many people were there and what did you do?

Alistair - This is a trial that we have recently announced the results of. It consists of 300 patients studied over 3 years. We are comparing the new drug against the standard licensed therapy of MS, which is beta inteferon. This is a head to head study saying “does this new drug alemtuzumab work better than beta interferon”? The results were that alemtuzumab is vastly more effective than beta interferon. It does three things, firstly it reduces the chance of having an attack of MS over three years by over 70% compared to taking the standard treatment. Secondly it reduces the chance of becoming disabled over three years by 70%. Both of those things we were expecting. The third result, which we weren’t expecting, is that at the end of three years patients who had taken alemtuzumab or CamPath were actually less disabled than they had been at the start of the study. So three years later they were now more able to work, more able to look after their families and more able to play their sports. That has forced us to go back and ask whether we really understand the disease of MS. Up until now people have always thought that once you have got disability from MS that is due to permanent scarring in the brain and that will never get better. We had imagined that the best we could get out of any treatment of MS is that people would just stay the same and not get any worse. Amazingly we now see people getting better.

Chris - What do you think is going on?

Alistair - We are back to the drawing board on this. One idea is that when the immune system recovers after being attacked by this drug, alemtuzumab or CamPath, immune cells grow back which are capable of getting into the brain and secreting factors that promote repair and survival of neurons and of the cells that produce myelin oligodendrocyte. That’s certainly not what we were expecting but we found it to be true.

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