Treating MS with Campath
What's actually going on in a person's body when they've got Multiple Sclerosis? Chris Smith spoke to Alastair Compston from the Department of Clinical Neuroscience in Cambridge where he specialises in dealing with this disease...
Chris - Tell us a bit then about when someone has multiple sclerosis, what is this disease?
Alastair - Well, Anthony gave a very clear account of the experience for a patient of attacks which come and go, with good long periods in between in which the patient is entirely well.
What he was describing was the patches of damage occurring from time to time in his brain and spinal cord. In those patches, a number of different things are happening. There's inflammation, there is some loss of the myelin sheath which is found around most nerve fibres in the brain and the spinal cord. There's damage to the nerves themselves. There is sometimes some repair and remyelination which we may hear about later, and there's scarring or sclerosis in those patches. So, multiple sclerosis, lots of areas of scarring and the problem has been to sort out what's driving that process, and how those different components fit together.
Chris - What is causing the inflammation?
Alastair - Well, this has been debated for many years and it's only really recently that I think most people would agree that inflammation is the primary process - the one that is driving the disease, and that comes from the circulation, from the lymphoid organs. It's not something which starts in the brain. What triggers it is complex and we'll probably discuss later some of the ideas around the causation of this inflammation, this autoimmunity which most people would not accept drives the disease.
Chris - So, immune system for some reason we don't quite understand moves into the nervous system and begins to attack certain patches of the nervous system, but by no means, all of it all at once.
Alastair - Yes, that's the idea. When that consensus was reached of thinking, then of course, it did offer the possibility of trying out treatments which might stop the immunological, inflammatory process and so, be useful for individuals who had the illness. But those ideas and the drugs which have been used really only started to come into play in the early 1990's. Since then a number of drugs have been licensed and they're used, and really, multiple sclerosis has been a fantastic success story in terms of the menu of drugs which can be thought about and used by comparison with many of the other diseases of the nervous system that we as neurologists deal with on a daily base. So, it has been very successful, but of course, there are still unmet needs and problems yet to be sorted.
Chris - So, the way that you'd chiefly tackle the disease is to try to damp down or turn off the immune response at least temporarily when it tries to flare up in order to stop it damaging the brain or spinal cord, wherever it's damaging at that moment.
Alastair - Well, that's my approach and I think most people would now agree that to tackle the immunological component is a very good way to start, both from theoretical reasons from what we know about the mechanisms of the disease and also empirically, from seeing what actually happens to patients when that approach is taken. So, all of the drugs that a neurologist can now think about using in people with multiple sclerosis are oriented around the immunological component. That's not to say that there aren't other aspects of the mechanism of the disease that we would like to deal with - neuro protection, remyelination and repair that we may hear about - but at the moment, the licensed drugs are addressing the immunological component because we think that is pivotal and driving everything forward.
Chris - Is that what led you to try this fairly radical drug Campath which was invented here in Cambridge which is a very potent way of removing the immune response at least for a period of time in some of your patients like Anthony?
Alastair - Well, when we first thought about using that monoclonal antibody, Cambridge pathology first human Campath-1H, the logic was that, yes, the disease is immunologically driven, but dealing with it once it's started and trying to unpick the events going on within the central nervous system was bound to be difficult. And so, our hypothesis was to ask whether we could go back a step and get outside the nervous system and deal with the process before the cascade of events had really set in.
So, the opportunity arose to do that because Campath is a humanised monoclonal antibody which targets the CD52 antigen which is present on all immune cells, T and B lymphocytes. It could be given by intravenous injection and there was every reason to expect that it would radically remove the immune system from the bloodstream and lymphoid organs, and then subsequently allow a repopulation with new cells, which we hoped would not bring back the old story of multiple sclerosis.
Chris - And is that what you found?
Alastair - It is actually what we found and we had to learn a number of lessons. It's taken us 25 years to get to the European license which was granted on the 17th of September this year. We've learned many lessons along the way, but we've ended up with clear evidence that the efficacy, in other words, the usefulness of the drug is very high. However, as with many treatments in medicine and multiple sclerosis is no exception, there is no free lunch. And so, with the very high efficacy, comes significant risks and hazards, and inconvenience of having to have injections and to attend hospital and to take part in risk monitoring schemes.
Chris - So, just very briefly, in someone who has MS and it was progressing in them, you put them in your Campath trial, what proportion of them are likely to achieve resolution of their disease like this and what sorts of side effects might they expect?
Alastair - Well, not quite and we have to be careful with this word 'progression'. So, multiple sclerosis starts with episodes which come and go, and then later, after some time, usually many years, those episodes dry up, reduce in frequency and are replaced by slow progression. We, in fact began by treating people with progression, with advanced disease who were already very disabled and we learned after a number of years - 7 or 8 years - that this particular drug and all others are not useful in that situation disappointingly. And so, in 1999, we switched to treating the disease very early in people who were threatened by multiple sclerosis but were still relatively well. And it was that switch from treating the disease late to treating the disease early that was the crucial step. And now that we do that, the experience is very good for most patients.