" What is research but a blind date with knowledge?"
~ Will Harvey
At least 60% of all MSers have Relapsing/Remitting MS (RRMS). It follows that most clinical trials apply to RRMS as well. The goal of these clinical trials is to slow or prevent slipping into the chasm known as Chronic Progressive MS. There is less known and fewer treatments for progressive MS types and also less research to address those problems.
There have been exciting news flashes about MS research with promising results. But we must be careful and not get too excited too quick. For example, stem cells are a favorite topic -- tests and treatment in other parts of the world seem to have positive results. Read Mandy Crane's article about a test in Chicago that stopped or reversed disability. She cautions readers because that test did NOT work for progressive.
So what is happening with research involving progressive MS? To be fair, there is more research concerning progressive MS now than there ever was before. If I search for RRMS at the clinical trials site, the response is a long list of trials. If, however, I search for SPMS, the advanced stage of RRMS, the page lists only a handful of trials; for PPMS, even fewer; and for PRMS there are none.
Research may be a clinical trial where the human element is added, or sometimes it is a study gathering and analyzing data from interviews and documented cases. A new research project may be expanding on treatments already approved for another disease, or it may be completely different. Let's look at some projects for progressive MS.
Secondary Progressive MS (SPMS)
Research for Secondary Progressive often centers around the fact that it is the advanced stage of Relapsing/Remitting and focuses on treatments already approved for the earlier stage.
MSers with SPMS often continue with treatment begun in their RRMS stage, but that is not always effective. A study to see if Betaseron is effective in SPMS found it to be true only when relapses still occurred. A Betaferon (called Betaseron in the U.S.) test, with a goal to determine if it is effective as progression sets in, has recently been terminated. A second Betaferon test is planned to determine disability progression, safety and adherence in daily use.
Researchers do not always rely on RRMS for SPMS research. An example of a new test that did not reach goals for RRMS, but is showing positive results so far for SPMS is Maestro-01 in Canada and Europe and Maestro-03 in the United States. Stopped for RRMS, it continues in its third and final phase for Secondary Progressive MS.
This study is based on two immune response genes in the autoimmune process (HLA types DR2 and/or DR4). Most MSers, 65%-75%, have one of these genes.
Further, there appears to be a need to study various vitamins and MS, at least Vitamins D and B3.
It has been known for some time there is a relationship between MS and Vitamin D, but the exact relationship is unclear. There is a Vitamin D deficiency in 60% of MSers, but more study is needed to determine how to correct that deficiency.
Then there is a question of Vitamin B3. In 2006, the National Multiple Sclerosis Society and the National Institute of Neurological Disorders and Stroke funded research that studied B3 in mice with positive results. They were published in the September 20 Journal of Neuroscience, and also promoted by the National Institute of Neurological Disorders and Stroke. "We hope that our work will initiate a clinical trial, and that nicotinamide could be used in real patients," the project head says. "In the early phase of MS, anti-inflammatory drugs may work, but long-term you need to protect against axonal damage."
These are only a few examples of ongoing Secondary Progressive research projects.
Primary Progressive MS (PPMS)
There are reasons it is difficult to fund and execute clinical trials for Primary Progressive MS:
* Fewer PPMS participants - Remember, only 15% of all MSers are PPMS
*Not ambulatory - Most MSers with PPMS are not walking
* Most are older - Likely to have problems that may interfere with the test
* Side effects - Greater measure of risk for easily affected MSers
* Unpredictability - Differences difficult to compare (speed of progression, plateaus)
* Financial - Lengthy test may be costly for testers and participants
Here is an example of a test that was terminated, but partially continued anyway. In 1999, the largest clinical trial for PPMS began testing Copaxone. An interim analysis found that almost 200 participants had quit and there was no significant response in women, so the test was terminated. However, there was response in men and since there was no treatment for PPMS, patients were offered the opportunity to continue. After three years analysis showed a significant slowing of progression in men.
There are trials that do continue to a natural conclusion. Here is an example of one that did not end prematurely, and it looks like a good one! UT Southwestern in Dallas where I happened to be diagnosed, is a teaching and research hospital, so I checked to see what they are doing for MS research. It has been designated as a lead site for a study of Rituxan, a therapeutic monoclonal antibody approved by the Food and Drug Administration in 1997 for treating some forms of cancer. This time it Is being tested specifically for PPMS.
"People with primary progressive MS don't respond as well to traditional drug therapies as patients with other, more common forms of the disease, such as relapsing and remitting MS. Because of this, many people with primary progressive MS have higher incidences of debilitating physical side effects." Kathleen Hawker, asst. prof of neurology UTSW. Not too long ago, it was questionable if the study would continue, but it overcame the obstacle and continued.
In February 2008, it was announced that Rituxan showed promise for MS. This test is interesting because it explores B cells rather than T cells. PPMS often begins in the spine rather than the brain, so maybe a different focus is needed here. The test was completed just this May, and the results should be announced soon.
Progressive Relapsing MS (PRMS)
It is difficult to diagnose Progressive Relapsing MS, and it is the least common disease course, so there are very few, if any, trials set up specifically for PRMS. However, MSers with PRMS often benefit from successful reseasrch for other MS types.
This type is often invited to participate in trials set up for other types, or trials such as cannibis-based where type does not matter.Another test valid for all types including PRMS is a recent on that asked "Does it hurt to smoke?" There seems to be evidence that smoking may exaggerate progression, and that is not a good thing. More study is needed, but it might be a good idea to quit ot at least cut down.
There are studies with goals other than new treatments. For example, there are studies to evaluate disability in relation to brain atrophy, or central motor conduction, and another comparing disability milestones with the patient's age at onset.
Open Clinical Trials
The final stage of research for a new medication is often volunteers taking it, tracking the results including side effects, and being monitored by testers to ensure the human factor produces the desired results.
My friend Denise was accepted for a clinical trial. "Things didn't quite work out as far as going on the trial/s went. Both trials I went for were for Secondary Progressive MSrs only. I didn't qualify for the first one, which was the stem cell trial. I was then passed on to a research team working on Statins - in this case Simvastatin. I decided not to go for this as the doses were just to high with potential side effects."
Denise brings up some good points. Volunteers must have exactly the characteristics for the desired outcome of the test. Also, each volunteer must carefully weigh the possible side effects against the benefits that may - or may not - result from taking the tested drug. In a placebo test, there is no way to know who is taking the test substance and who is taking the control.
Here are some clinical trials accepting volunteers:
- Oral Cladribine with Interferon-beta for SPMS, safety, tolerability, effectiveness
- Betaferon (Europe's name for Betaseron) for any type MS, disability progression, safety, daily adherence
- Betaferon for PPMS, disability progression, safety, daily adherence
To find these and other new studies and keep up with the status, visit Clinical Trials.
The National MS Society is always a good source for information. They provide a good article on Reseaerch in Progressive MS. In addition, they provide a downloadable pamphlet of 129 clinical studies that are current, just completed, or planned to begin in 2009.The MS International Federation also publishes information on MS research around the world.
Notes and Links
I appreciate the help of Facebook friend Denise Walburgh.
Some of the links are short, dry notices; they provide links to more detail.
NMSS downloadable 2009 clinical trials
MSIF progressive research
Primary Progressive MS and research
Current clinical trials
Published On: June 10, 2009