• Published:November 21st, 2008
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• Category:Uncategorized

Last week several of us attended the annual fund-raising lecture and dinner at our local hospital, for which the PHG Foundation was a sponsor. This year’s Addenbrookes Annual lecture was given by Professor Alastair Compston, and titled Treating multiple sclerosis: a modern saga. One of the undeniable benefits of Cambridge is the constant proximity to cutting-edge research in medicine and the biomedical sciences (yes, I suppose in a few other things as well - but research involving hadron colliders and all that just isn’t as much fun, to my mind). PHG Foundation headquarters is five minutes stroll from the Cambridge University Hospitals NHS Trust site, which incorporates both Addenbrookes and a whole bunch of major research centres.

Multiple sclerosis or MS is not a disease that I have worked on, or indeed learned much about since studying pathology as a student quite a long time ago (Long in terms of biomedical research, anyway. OK then, it was 12 years ago), and so I was brought up to speed, in very general terms, with progress in understanding the molecular basis of the disease. Professor Compston and colleague Dr Alasdair Coles have also just produced a handy review on MS [Compston A, Coles A (2008) Lancet. 372(9648):1502-17], or for those who want to know more but in simpler terms, the UK MS society website has some information.

The main focus of the lecture was the story of Campath1 /alemtuzumab, the first humanised monoclonal antibody produced as a therapeutic agent (ie. treatment). Although it was originally produced with quite a different disease in mind, Professor Compston and colleagues reasoned that, since the neuronal damage in MS was the result of an inappropriate immune reaction (as with other forms of autoimmune disease), perhaps a drug that attacked immune cells might be an effective treatment. Some people with advanced forms of the disease received it, and showed significant initial improvement but didn’t do well longer term.

However, the researchers then tried the treatment in people in the early stages of the disease - when the insulating myelin sheath that normally protects neuronal cells and allows rapid transmission of impulses was being lost, but before the neurons themselves had been destroyed. It had some very grave side-effects, so that the trial of the treatment was truncated, with most patients not receiving the third planned administration of alemtuzumab. However, looking at the final results of the study it was shown that the patients who had received alemtuzumab had done much better than the control group who received standard therapy; not only had they had far fewer symptomatic attacks, but they generally also showed that their overall condition had improved over the course of the trial.

What struck me particularly was that the patients in this trial - whose enthusiastic personal endorsements of the striking benefits to their quality of life from the treatment could not fail to move even those of us for whom the key word in ‘fund-raising lecture and dinner’ had been ‘dinner’ - knew the risks of treatment. Quite a substantial proportion developed other types of autoimmunity and some, cancer; one patient died. But the adverse impact of MS on some patients before entering the trial had been very severe, and they had clearly thought it was worth the risk. Makes you think about the ethics of regulation of experimental treatments, really. I suppose the same patients would have been less enthusiastic had the treatment turned out to be unsuccessful. But it does seem to me that a certain degree of risk and bravery on the part of patients, clinicians, funders and regulators may be appropriate. Nothing ventured, nothing gained?

And if you think I should have said more about the genetics of susceptibility to MS, other researchers have just found the first genetic variant associated with disease risk to be expressed specifically in neurons, within the KIF1B gene: [Aulchenko YS et al. (2008) Nat Genet. Nov 9, epub ahead of print]. Gene variants previously associated with disease susceptibility have been involved in immune function.