When I wrote that I was coming to ECTRIMS 2011 to report on the most current MS treatment and research on the disease, I got several e-mails and blog comments from people with primary progressive MS (PPMS), who were anxious to hear what treatment was in development for them. My friends, I wish I had better – indeed, any – news to report. At this conference, there was no research presented about developments in treatment of PPMS.Why the huge disparity in research activity around treatment for relapsing-remitting MS (RRMS) and PPMS? Of course, the first thing that comes to mind is that PPMS treatment has much less potential for huge profit than a successful RRMS drug, due to the fact that only 10 to 15% of people with MS have PPMS, with the vast majority having RRMS.
Saturday, October 22, 2011
Where is the PPMS research at ECTRIMS 2011?
I won't lie to you – the bottom line is definitely a factor. However, there are other big challenges to running trials to test medications specifically for PPMS, though. Many of these have to do with designing a study that would give any meaningful results. Remembering that virtually every clinical trial is complicated by difficulties in recruitment, follow-up, unexpected side effects, adherence, etc., which makes any clinical trial a huge and expensive undertaking. Even for a motivated group of researchers, any of the characteristics of PPMS as a disease and the population with PPMS make trials even more daunting.
Disability: Many studies require people to be ambulatory (able to walk) in order to be included in a study. This is so that the effect of the study drug on walking ability, energy level and other physical abilities can be studied by having people walk a certain distance within a certain time. In this way, researchers can use scores on the Expanded Disability Status Scale (EDSS) as an outcome measure. Many people with PPMS are no longer ambulatory.
Age: People with PPMS tend to be older, meaning that they often have additional age-related health problems, such as cardiac issues, diabetes, high blood pressure, vision problems and others. This makes it more difficult to determine which disease (MS or one of the other ones) is causing or contributing to disability. It also makes it difficult to determine which symptoms are side effects from the study drug and which are due to underlying health problems. In addition, people with other conditions may need to take other medications, which would exclude them from the study, as interactions between medications would not be known or could interfere with results.
Side Effects: It may be harder for people with PPMS to tolerate side effects from the study drug, both due to MS-related symptoms, other health issues and age.
PPMS Is Unpredictable: PPMS behaves differently in different people — some people experience a very quick progression to disability and others progress very slowly, often experiencing “plateaus” of several months or even years where symptoms remain stable. This variability makes it very difficult for researchers to compare placebo groups to treatment groups.
People whose PPMS progresses very slowly may have to be eliminated from the study so that researchers could figure out if the drug is doing anything (otherwise the study would have to continue for many years). That would leave only the people with quickly-progressing PPMS, though, which would also not be a good test of a drug, as these cases may not be representative of all (or even most) cases of PPMS.
Basic Research is Being Done: All of these points are just to illustrate why research on PPMS treatment is very difficult. However, this does not mean that scientists are ignoring PPMS. There are some studies in very early stages, many still in animal models, exploring treatments that regenerate and rebuild myelin and lost axons, as well as studies on DNA and other biomarkers that will eventually guide treatment.
In addition, researchers are starting to explore different technology, such as triple-dose gadolinium, and more powerful MRI scans to learn more about the effects of PPMS that have been difficult to assess until recently. I would have loved nothing more than to bring news to you about a "breakthrough" in treating PPMS, hopes are that these developments will eventually help in the search for effective therapies for people with PPMS.