Professor Giancarlo Comi, San Raffaele MS Centre, Milan, Italy and Professor Per Soelberg Sørensen, Danish Multiple Sclerosis Centre, Copenhagen, Denmark, consider the stages and the transitions of MS during disease progression. They also discuss some of the most promising biomarkers and how a better understanding of disease progression measures will inform treatment decisions.

Giancarlo Comi: Well first of all MS is a two-phase disease. There is the first phase characterised by lesions that attack the central nervous system and the second phase where what happens is a degeneration of the tissue which is mostly independent from these initial lesions, partially, not completely independent. So, the mechanisms that are determining the damage are quite different in the two phases. What is very important is to try to capture the time where the patient shifts from relapsing to progressive. So, then the key point is, is there any possibility to predict the risk of progression in a patient with multiple sclerosis, and the answer is yes. And these predictors are very important because then we may use these also to see if we are able with our treatment to modify the risk.

Per Soelberg Sorensen: So, if we have reliable disease progression measures then we would be able to choose these patients who require an effective treatment from the start and those who can start with a more moderately effective treatment.

Giancarlo Comi: There are some factors that predict an earlier evolution to progressive MS. These factors are the amount of lesions in the spinal cord. Probably best to do also a bit with the way we measure disability progression and the high level of this scale, is the amount of lesions in the grey matter, cortical lesions are also very important in terms of prediction, is the amount of damage of the pathways, as revealed by a combination of evoked potential. Evoked potentials estimate which is the rapidity of travel of waves in our body along the nervous pathways, the more the pathways are damaged the more these type of connections are not functioning well. There are some new MRI techniques that estimate that the tissue damage which are really very, very interesting for the future evolution and there are also other aspects, for example the amount of damage revealed by the analysis in the blood of the neurofilaments that are pieces of the neuron, that when the neuron is destroyed are delivered and then can be found in the blood.

Per Sorensen The only thing that is close to coming into clinical practice of biomarkers is the neurofilament in the blood because we can’t make CSF examinations repeatedly in most patients, so we need to have a biomarker that can be measured in the blood and the neurofilament is absolutely the most promising. We just made a register study where we looked at patients who had started treatment very early after the diagnosis and after the first symptom of MS and compared them with those who had a delay and there was a 40 percent difference in the risk of reaching EDSS 6 meaning losing gait function so we need to treat treatment, we need to use the right treatment from the start.