Until recently, it was thought that disability in MS was caused mainly by the gradual loss of the fatty insulating layer of myelin which surrounds nerve fibres (axons), and which allows them to conduct electrical signals. However, we now know that most of the permanent disability in MS occurs because the axons themselves degenerate.

Experience suggests that the current strategy of modifying the immune system may not be able by itself to prevent this axonal degeneration and consequent disability, and that we will need to develop a second strategy, called neuroprotection, to achieve this goal. In order to do so, we will need to identify and to inhibit the mechanisms by which axons are damaged.

Research work has already identified several such mechanisms. For example, our group has shown that axons may be flooded with toxic levels of sodium from the surrounding tissue fluid as a result of inflammation in MS, and that the resulting damage can be prevented by drugs which reduce the entry of sodium. As a result, we have been awarded a grant by the Multiple Sclerosis Society to carry out a clinical trial to test the neuroprotective effects of one of these sodium channel blocking drug, lamotrigine, in people with the secondary progressive form of MS. We will randomize people in the trial to receive treatment either with lamotrigine or with an identical placebo (i.e. dummy) tablet for two years.

We will be able to compare the effect, of lamotrigine with the placebo, on the gradual shrinkage of the brain caused by axonal degeneration.  This will be done by carrying out MRI scans at regular intervals. We will also measure the actual levels of disability in the two groups to assess the extent to which the treatment slows down its progression. This is likely to be the first of a number of trials which seek to block axonal degeneration by inhibiting the mechanisms by which the axons are damaged, and which offer new hope of treatments which can prevent people with MS from becoming disabled.

Clinical Trials of cannabinoids as neuroprotective agents in MS

Professor John Zajicek, from the Peninsula Medical School in Plymouth, outlined the reasons for believing that some cannabinoids (chemicals derived from the cannabis plant), may be useful in the long-term management of MS.

The believed effectiveness partly stemmed from the long-term results from the CAMS study, where people who took oral THC capsules over a 12 month period seemed not only to have less stiffness than those on placebo drugs, but also less disability.

There is now quite a lot of experimental evidence from laboratory work, both in the test tube and in animal models, showing that cannabinoids may help to protect the nervous system, and facilitate survival of both nerve cells and oligodendrocytes that produce myelin sheaths. This background evidence combined with the long-term results from the CAMS study has led to the Medical Research Council funding a new long-term study of cannabinoids known as the CUPID study (cannabinoid use in progressive inflammatory brain disease). The MS Society are also helping to fund this study, which will be starting in early 2006.

CUPID will recruit 500 people with progressive MS and ask them to take either THC or placebo capsules for 3 years, during which time measurements looking at disease impact and disability will be made by researchers and patients.

For more information on this study visit http://www.pms.ac.uk/cnrg/cupid.php