Understanding and treating progressive MS: A conversation with Dr. Peter Calabresi
National MS Society: Dr. Calabresi, you’ve conducted clinical trials in MS and have treated people with MS for many years. Can you help us understand why there aren’t more treatments for progressive MS?
Peter Calabresi: Well, it’s not for a lack of trying. We’ve used all of the FDA-approved drugs that are indicated for relapsing MS in progressive MS and so far they haven’t worked, although some of those trials are still ongoing.
But I think the real issue is that progressive MS may be different than relapsing MS. By that I mean that in relapsing MS we know that there’s inflammation, and we know how to target inflammation. But in progressive MS there’s likely a different process going on. The nerves themselves become unhappy from the loss of myelin, and we need to figure out how to rescue those nerves and keep them happier and target remyelination.
The Society: People want to know what can be done to stop MS progression. You’ve been researching ways to protect the nervous system from damage in MS. What have you and others learned?
Calabresi: It’s a challenging problem, but we’re looking at how nerve cells survive and the signals that are required to keep them alive. First, we’re screening drugs, compounds that may be already available in a drug that’s already indicated by the FDA for one disease. Second, we’re also trying to find out how we can repair the tissue, through remyelination, and really are just starting to get ideas about how to do that. We do know that within all of our brains there are cells that have the capacity to turn into myelin-making cells. If we can figure out how to turn these cells on and get them to turn into myelin-making cells, we could actually repair the brain in progressive MS.
The Society: We recently awarded you with a Collaborative MS Research Center award to find ways to repair damage. Tell us a bit about that collaboration and how this helps tackle such a hard problem?
Calabresi: I think nervous system repair is so hard because there are a lot of different things that may be happening in different patients. The idea with the Collaborative Center award approach is that we tap into expertise of scientists from other areas of medical research. We’re working with a biologist, Dr. Dwight Bergles, who specializes in how myelination happens in the first place. Using tools he’s developed in his lab, we can now better understand how age affects myelination so that we can make myelin again in older people and then apply that to others. It’s a bit like dialing back the clock to make our bodies think that we’re children again and we need to myelinate. And through understanding how it happens normally, we can perhaps trigger that to happen in patients with MS. We’re also working with Dr. Jeff Rothstein who is working on ALS, or Lou Gehrig’s disease, another disease where there’s brain degeneration. It’s very important that we understand lessons that have been learned from that disease and apply them to MS. It is an exciting time, and I think this kind of collaboration is really critical to making progress and moving forward quickly.
Society commits $18 million to drive solutions for MS
Frequently I hear from people with MS, or their loved ones. “Why is it taking you so long to find a cure?” or “How can you be sure you’re funding the most important research?” I share their sense of urgency for solutions to be developed for everyone impacted by MS. At the same time, I am confident in the research the Society funds due to the force powering funding decisions — our scientific advisors, who collectively volunteer more than 5000 hours annually to review research proposals. The Society relies on the advice of these leading scientists, physicians and other experts from virtually every field related to MS to help us make decisions about which research projects and programs have the best chance of moving us closer to a world free of MS. Out of their recommendations, we have just committed to support up to 53 new research projects, training fellowships and special initiatives totaling over $18 million. These are part of our $45 million international investment in over 325 cutting-edge research projects, this year alone. It’s by each of us doing our part — experts identifying the most promising and important research, people with MS participating in clinical trials and everyone who can generously supporting this work — that we will achieve a world free of MS.
Cyndi Zagieboylo
President & CEO
National Multiple Sclerosis Society
Four research projects you should know about
The Society has just committed to supporting up to 53 new research projects, training fellowships and special initiatives. These important projects will cost over $18 million, and we’ve pledged to raise the money to make sure they will proceed. Below are some of the important issues being tackled by these researchers, which build on new discoveries and advances in technology:
STOPPING MS
Why do people with MS stop taking their treatments?
In this project Dr. Helen Tremlett, University of British Columbia, is trying to find out if MS progression and other aspects of health are different for people who take their disease-modifying therapies as prescribed compared to those who stop taking their treatments. Project Cost: $286,059
RESTORING FUNCTION
Why do people with MS experience pain?
In this project Dr. Heather Wishart, Dartmouth College, is using advanced MRI techniques to determine what parts of the brain are associated with pain in MS. This will help health professionals as they develop strategies
to improve pain management and prevention in MS. Project Cost: $300,236
What can we learn from studying patients who’ve participated in clinical trials for MS therapies?
In this project Dr. Robert Naismith, Washington University, is studying patients who participated in a clinical trial comparing Betaseron and Copaxone. He is applying advanced imaging techniques and mining valuable data from previous clinical trials to evaluate nerve injury and repair, and to show whether enhanced imaging may be useful for evaluating new therapies. Project Cost - $416,565
ENDING MS
Why do we collect genetic material?
In this project Dr. Jorge Oksenberg, University of California, San Francisco, is leading a team who are collecting and storing genetic material from individuals and families with MS, and linking them to a database with clinical, demographic, and laboratory data. This is a vital, shared resource for studies searching for genes that contribute to the risk of getting MS. Project Cost: $1,560,377
What is the National MS Society doing for Progressive MS?
Timothy Coetzze, PhD
Chief Research Officer
People with progressive MS often tell me that they feel like they’re being left out of the progress made in MS research and treatments. I certainly understand their frustration, but am excited to report that the National MS Society is working harder than ever to overcome this hurdle by implementing bold new approaches. We are mapping a course of action to move this work forward quickly. Here are the priorities we are pursuing:
Determine what is causing progression
MS progression can be slow or it can be fast, but it occurs in many people who have MS, even in people successfully treated for relapses. We need more research to better define and understand the basic mechanisms of how the progression happens.
Jump start MS clinical trials
Our research is focused on discovering new therapies, designing new ways to conduct clinical trials and to speed up the testing of promising therapies. We’re building on the momentum from Promise: 2010 (see box below).
Train new MS scientists & investigators to propel ongoing research
We are committed to attracting and retaining the brightest minds through offering fellowships, career transition and faculty awards via our training programs.
The Society is also part of a global collaborative seeking to propel specific elements of this work. There is a lot of work to do in progressive MS, but we are seizing unprecedented opportunities to achieve advancements that will make a big difference in people’s lives.
Meet Elissa J. ("EJ") Levy
In the summer of 2001 I was living in San Francisco. I remember being out on an afternoon hike and I kept tripping. My friends and I laughed at how clumsy I was. The next day when I kept falling out of positions in yoga class, I knew there was something wrong.
Six months later I was diagnosed with secondary progressive multiple sclerosis. Unfortunately, my disease progressed quickly and within two years I went from an active healthy young woman who loved to ski, hike, travel and spend hours at the gym to someone who could barely walk a couple of blocks even with a cane.
I needed to use a wheelchair for long distances but spent most of my life on my couch. I went from working full time, to four days a week, to two days a week, mostly working from home until finally I went on Long Term Disability. As soon as I was diagnosed, my doctor put me on a disease-modifying therapy but it didn’t help. We tried other therapies, but my MS continued to progress.
Then my doctor told me about an experimental medication called 4-AP. It sat in my medicine cabinet for 2 months because I was so tired of trying things that only made me feel sicker and didn’t seem to have any benefit. Finally I built up enough courage to try one more; a week later I went to see my doctor. He would test the strength of my leg and hip flexor, by having me lay flat and then try and raise my right leg as high as I could. Usually I could raise my leg 1–2” off the table, but that Friday my leg flew 90° into the air! My doctor and I stared at each other. Then I started to do Rockette kicks up in the air and I finally jumped off the table and started to walk around, smiling and waving and doing kicks for everyone. When I went back into the exam room, I burst into tears and although my doctor will not admit it, he was crying too.
The feeling of being able to easily walk again, after four years of barely being able to move my leg, was incredible. I went and told everyone about the treatment that gave me my life back. A couple of years later I was fortunate to testify in front of the FDA to help get 4-AP approved as Ampyra. When my doctors refer to the effects Ampyra has had on me, they call me a “super responder.” Unfortunately not everyone has had the same response, but it does help many to different degrees.
I am so passionate about raising money for research because I want everybody living with MS to find his or her “magic pill.” MS is a very complex disease and it’s unlikely that we will find one answer that will help everyone. We need to raise as many research dollars as possible so we can bring as many therapies to the table — so that everyone can have a success story like mine. Through my foundation, MS Hope for a Cure, I have raised and contributed nearly $1 million dollars for the Society to help fuel the research pipeline. Today I am a member of the NOW Campaign Cabinet and have pledged another $1 million to fund research while I continue to mobilize others to donate as well.
