Trends in MS research: New antigen-specific treatment approaches - individualised therapy remains key goal

"This first EAN Congress is providing a major opportunity for the multiple-sclerosis community to interchange research interests. We are witnessing a number of very good quality sessions and presentations which reflect the amazing evolution in MS research and therapy," Prof Xavier Montalban from the Vall d'Hebron Hospital in Barcelona, President of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), said at the 1st Congress of the European Academy (EAN) in Berlin. "Among the important developments in our dynamic field are the constant expansion of therapeutic options, focus on the potential of individually tailored therapies and new approaches towards antigen-specific immunisation."

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterised by a high degree of heterogeneity. Around 500,000 people in Europe suffer from this degenerative, progressive autoimmune disease, with two to three times as many women affected as men. It is most often diagnosed in people aged 20 to 40. In young adults, along with epilepsy, MS is one of the most frequent neurological diseases, and a major cause for disability in this age group. The overall cost of MS to European health and social-care systems is estimated to be 15 billion euros a year.

Decoding the mechanisms of MS pathogenesis

Among the issues that are of particular interest to MS experts around the globe is a better understanding of the pathogenesis of the disease, which is currently still incomplete. "Deciphering the underlying pathomechanisms, elucidating the precise mechanisms of tissue damage in relapsing-remitting MS and establishing the relative role of these processes in irreversible tissue damage in progressive MS are key aims of ongoing MS research," according to Prof Montalban. This might open the path to identifying new treatment targets that can help halt disease progression or even to developing regenerative treatment approaches.

Personalised treatment one of the "most unmet-needs areas"

"Nowadays the number of treatments available for MS with different mechanisms of action is quite impressive. There is a well-founded reason to say that we will be able to help people suffering from MS ever more effectively and more quickly," Prof Montalban commented. A broad range of new results on classic injectable drugs, new oral substances and monoclonal antibodies as well as future treatments, including neuroprotective and remyelinating agents, are being discussed at the EAN Congress.

The broadened range of therapies available generates questions as to the positioning of each substance and the development of additional algorithms, but might also facilitate a truly individualised therapy approach, Prof Montalban explained: "Personalised medicine is one of the most unmet-needs areas we have in MS nowadays. To understand the prognosis of a specific patient, to choose the best possible treatment for that patient and to predict the effects and side-effects that a specific drug might have in this individual are not easy exercises. But there is growing evidence, including data on biomarkers, which supports us in this task."

A promising new approach to immunisation

"The role of antigen-specific tolerance and the possibility that antigen-specific therapy may eradicate unwanted adaptive pathologic antibody and T cell-mediated immune responses that damage tissue while preserving the normal immune function responding to infectious agents and retaining the ability to fight malignancy are among the innovative and exciting approaches in MS therapy that are being discussed at the EAN Congress," Prof Montalban reported. "We do not yet have very convincing evidence in MS that would prove a dominant immune response to a specific antigen or group of antigens. However, a more specific antigen-driven disease such as neuromyelitis looks like quite a promising model for this concept of therapy."

The presentation of data from the ETIMS trial at the EAN Congress was a subject of interest. "In brief, coupling autologous blood cells chemically with seven myelin peptides to induce antigen-specific tolerance was tested in an open-label, single-centre, phase-I trial," Prof Montalban explained. "The feasibility, tolerability and safety of this novel therapeutic approach were established. A multicentre proof-of-concept phase-IIa trial is in preparation."

Another approach in this field might be the use of patches to administer specific myelin peptides in order to influence immune response in MS patients, Prof Montalban reported. "A very impressive trial conducted by a research group form Lodz, Poland shows the immunoregulatory potential of transdermal immunisation with myelin peptides in MS patients. In a double-blind phase-1 trial in 30 patients with RRMS a significant reduction in MRI and clinically measured disease activity was observed, opening a new window for different ways of drug administration, again based on the concept of immune tolerance", Prof. Montalban explained.

Neuroprotective potential of vitamins and antiepileptic drugs

A high-dose vitamin and a substance so far used for its antiepileptic properties might both have potential as novel treatments in MS, as shown by two trials presented at the Berlin Congress. "One study using biotin in progressive MS and another using phenytoin in optic neuritis both show signs of having neuroprotective effects that warrant further studies," stated Prof Montalban, commenting on the preliminary findings.

Understanding risks and benefits

Another focus of particular importance, according to Prof Montalban: "Effectiveness in real life and also data coming from extension studies of a number of drugs are being presented and discussed. This clinical and imaging information is essential in understanding the benefit/risk ratio of any drug." Among the myriad results in this field, a late-breaking result on magnetic resonance imaging outcome for patients who switched from interferon beta-1a to alemtuzumab has been presented at the EAN Congress. It shows that the switch improved MRI outcomes in patients who received more than two years of prior disease-modifying therapy.

Data on the long-term history of untreated MS are very scarce, although of great interest to the research community. At the EAN Congress, a Swedish research team has presented a 50-year follow-up study of an incidence cohort of Gothenburg residents with onset of MS between 1950 and 1964, providing prognostic and outcome data in untreated patients over several decades. "This very interesting paper indicates an increasingly benign course of MS," Prof Montalban said. "These data, very difficult to obtain, are really useful in our decision-making processes."