Clinical research group:
Per Soelberg Sørensen, Morten Blinkenberg, Finn Sellebjerg, Annette Oturai, Ana Voldsgaard, Karen Schreiber, Henrik Mathiesen, Melinda Magyari, Lars Bornsen, Jeppe Romme Christensen, Rikke Ratzer, Julie Maria Hejgaard, Eva Rose Petersen, Cecilie Ammitzbøll, Anja Thormann, Vibeke Jespersen, Joan Pietraszek, Sidsel Walther Nielsen, Anne Hansen, Annette Larsen.
In 2011 we published the results of the SIMCOMBIN study, which is a Nordic multi-centre study directed from DMSC and conducted in 42 MS Centres in Denmark, Norway, Sweden and Finland. The study investigated simvastatin as add-on therapy to interferon-beta in de novo treated patients with relapsing-remitting MS. More than 300 patients participated in the trial. Unfortunately the results showed that there was no benefit of add-on of simvastatin to interferon-beta.
We have in 2011 completed another combination treatment trial, which is a multi-centre European trial exploring the effect of Minocycline as add-on therapy to interferon-beta in de novo treated patients. The trial showed no statistical significant beneficial effects of Minocycline as add on to interferon-beta although there was a weak trend in many of the primary and secondary endpoints.
We are currently performing several single-centre studies in patients with progressive MS in order to try to find treatment options for this phase of the disease that currently lags effective therapy.
We have recently concluded a study on the effect of Erythropoietin on disability in 56 patients with progressive MS. Data are currently being analysed and we expect to publish the results in the autumn 2014.
We have performed a small safety study with eggs of the pig whipworm (Trichuris suis) taken orally every 2 weeks. This small trial has been completed, and the data was presented at the American Academy Meeting in April 2012. Unfortunately, we could not show any beneficial effects of treatment with Trichuris suis eggs neither as add- on to interferon-beta therapy or as mono-therapy. Hence, in the light of the negative results we have abandoned the start a larger phase II trial with inclusion of 80 patients.
We have completed a small study investigating the in vivo biological response to interferon-alpha in MS patients, who have developed neutralizing antibodies against interferon-beta. We are able to demonstrate that a number of genes, which usually respond to injection of interferon-beta, could be elicited by injection of interferon-alpha, although the patients no longer had a response to interferon-beta. Hence, interferon-alpha could be a therapeutic option in these patients.
Furthermore, we have conducted an exploratory trial of natalizumab (Tysabri) in patients with progressive MS. Natalizumab had a significant on markers of inflammation and neuronal damage in the cerebrospinal fluid. The results indicate that inflammation in the peripheral immune system may contribute to disease activity and progression in patients with progressive MS.
Recently, we have concluded a similar trial investigating the effect of monthly cycles of methylprednisolone tablets. The data are currently being examined.
In addition to these investigator-driven therapeutic trials, DMSC is taking part in clinical trials of new drugs sponsored and driven by the pharmaceutical industry. We are currently involved in trials of new indications for treatment with fingolimod, and we are involved in the development of three new monoclonal antibodies alemtuzumab, daclizumab, and ofatumumab with strong effects on disease activity. We are involved in a trial of fampridine on improvement of gait function and quality of life in patients with MS and impaired gait function.
Other clinical research trials
In collaboration with the Danish MS Register we performed a study of changes in prevalence, incidence, and sex-ratio through the last decades and observed increased incidence rates, apparently confined to women, and demonstrated the dismissal of a true latitudinal gradient on the northern hemisphere.
The collaboration has continued and we have been involved in the investigation of the cause for the increasing incidence of MS in women. We have shown that childbirth has a protective effect lasting for at least 5 years. We are currently investigating the effect of factors in physical and social environment on the susceptibility to MS and have initiated a study on the susceptibility and clinical cause of MS.
In 2010 we initiated a study exploring the role of vitamin D on clinical disease activity in MS. Vitamin D seems to yield some protection against encountering MS and may also influence the disease activity in established MS. DMSC is among the leading centres in the world regarding studies of antibodies against biological agents.
We have extensively studied the effect of neutralizing antibodies against interferon-beta, most recently in an EU supported European study of neutralizing antibodies against interferon-beta (NABINMS study). We have introduced a new assay for detecting neutralizing antibodies based on a luciferase reporter gene under control of interferon-beta, and we have recently studied the relationship between antibodies binding to interferon-beta and antibodies neutralizing interferon-beta.
Recently, we have published the results of an international study of the frequency of occurrence of antibodies against natalizumab together with MS centres in Sweden, Norway and Germany. We were able to show that fewer patients developed persistent antibodies against natalizumab compared with the observation in clinical studies. We have also shown that the propensity to develop antibodies against interferon-beta does not carry an excess risk of developing antibodies against natalizumab.
We have concluded a study of titres of antibodies against natalizumab and have demonstrated that the titre already 3 months after start of natalizumab therapy predicts if a patient will develop permanent antibodies against natalizumab and, therefore, would have to stop natalizumab therapy.