Greetings from Philadelphia! You might remember that Philadelphia was our Nation’s capital during the revolutionary war. This week, the city of brotherly love is the capital of multiple sclerosis research as thousands of neurologists gather here to report their latest discoveries.
I have been impressed by both the number and the quality of studies on emerging therapies for MS being presented this week. One of these studies was the eagerly awaited clinical trial of the pregnancy hormone estriol combined with Copaxone in relapsing-remitting MS. This study was inspired by the observation that MS relapses are less frequent during the third trimester of pregnancy, a time when estriol is at its highest level. In this trial of 164 women, the investigators determined that pregnancy levels of estriol plus Copaxone reduced the rate of relapses after one-year by 47% compared to women taking Copaxone alone. There were also significant positive benefits observed in the scores of cognition tests. These positive effects were less significant in the second year of the study – the reasons why are not clear, but a more thorough analysis might reveal some answers.
The “hygiene hypothesis” proposes that the increased frequency of autoimmune diseases like MS in industrialized countries is due to a reduction in exposures to infectious bacteria, viruses and parasites. This hypothesis gave rise to a study reported by a team of investigators from the University of Wisconsin. Participants in this trial drank a sports drink laced with the eggs of a pig parasite called porcine whipworm every two weeks for ten months.
The number of active brain lesions detected at the end of the trial by MRI was moderately reduced by 34% compared to the number lesions detected at the beginning of the trial. Evidence was also presented that treatment could promote the activity of disease-suppressing white blood cells. This was a small trial and needs to be repeated in a larger number of participants before definite conclusions can be made. Imagine if we could treat MS with a sports drink?
Of all the many different industry sponsored clinical trials being presented this week, one that in particular intrigued me was a phase II trial testing a biological agent called Ofatumumab (who comes up with these names!) in MS. Ofatumumab targets a type of white blood cell called a B cell and is already approved for the treatment of B cell cancers. Previous studies suggest B cells play a role in MS disease activity, so getting rid of them may reduce relapses and help slow disease progression.
The study investigators reported a 65% reduction in the number of active brain lesions detected by MRI in the treated groups compared to the placebo groups – pretty impressive. These results add to previous studies with related agents and suggest targeting B cells is a very promising approach for treating MS.
Finally, something to keep your eye on for the future. IRX4204 is small molecule that selectively inhibits the activity of a receptor, or docking site, for a Vitamin A-like molecule called retinoic acid. Two studies presented this week suggest that IRX4204 may inhibit inflammatory responses and promote the repair of myelin, the nerve fiber casing that’s damaged by MS immune attacks. If true, this one-two punch could be a powerful combination that would both stop immune responses that lead to nervous system damage and also repair what has been lost. These are early stage animal model studies and must be followed up in people with MS before we get too excited, but I find the strategy to pursue agents with both anti-inflammatory and repair properties pretty exciting.
That’s it for now. I have to rush off to the next session (and a Philly cheesesteak sandwich). Stay tuned for more posts coming soon.