Associate Professor Mark Slee, neurologist at Flinders Medical Centre and Vice-Chair of MS Research Australia’s Research Management Council, has provided this report on the first day of the formal ECTRIMS program.
ECTRIMS opened with a lecture delivered by the outgoing ECTRIMS President Xavier Montalban, he covered areas like personalised decision making in relation to MS treatments, focusing on the need for highly predictive biomarkers to aid clinical decision making as well as aiding the acceleration of clinical trials. Biomarkers are also important to understand the risk of disease progression and the risk of treatment side-effects, for example JC virus status and how this relates to risk of progressive multifocal leukoencephalopathy (PML), a serious brain infection that can be increased when immunosuppressive medications are used.
The morning program included a terrific session reviewing the evidence for involvement of the innate immune system in MS pathogenesis. This involved, among other things, data on the role of dysfunctional phagocytosis in MS (a mechanism used by the immune system to remove bacteria and debris from tissues), the pro-inflammatory role of a molecule that is normally involved in blood clots, called fibrinogen, and the role of a particular type of immune cell, known as dendritic cells, in MS.
In the afternoon, a session was held reviewing the possible role of energy deficits in the cell in MS. In particular, the role of mitochondria and the emerging role of sodium accumulation in the body, including the brain and spinal cord in the disease.
To end the day, there was a balanced and considered debate on the role of autologous haematopoietic stem cell transplant (AHSCT) in MS. AHSCT is a controversial treatment option, with early trials showing high levels of toxicity. It is important with such an invasive treatment to know that the majority of patients will benefit. The consensus in the debate was that there is limited but solid data to suggest AHSCT has a beneficial effect in highly active relapsing remitting MS, in young patients (less than 45years) and with low disability levels (less than EDSS 6) and a low total disease duration. Early toxicity has been steadily reducing since 2005. Even with high intensity regimens, 30% of patients experience disease progression but the rate of NEDA (no evidence of disease activity) is high. A metaanalysis of all published trials by Maria Pia Sormani is in press.
It is important that this studies into the AHSCT continue. So it is pleasing to hear of aa planned phase III Italian study of people with relapsing remitting MS who have failed 1-2 platform therapies in which they will be randomised to AHSCT vs best other therapy. However, it was stated at the end that the clinical trial that is most needed is to compare people with early active relapsing remitting MS who have not had any treatment or have failed only 1 therapy who are given either ASHCT or a highly active therapy (such as natalizumab, or alemtuzumab). However, this trial but must be multi centred and have adequate patient numbers to show an effect. This will be difficult given there is no consensus on the optimal AHSCT regimen or ex-vivo graft manipulation. There is indirect evidence that patients with progressive MS (of any type) do not respond favourably to AHSCT although the only way to determine this definitively is to undertake well designed clinical trial.