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Reflecting Back and Looking Ahead

Since 2008, Dr. Timothy Vollmer has not only been one of the primary neurologists seeing patients at the Rocky Mountain MS Center at University of Colorado, but has also served as Co-Director of RMMSC at CU and as the Medical Director of the Rocky Mountain MS Center nonprofit organization. Earlier this year, Dr. Vollmer announced his retirement, effective at the end of 2021.

Dr. Vollmer has cared for thousands of MS patients over the years, and has played an instrumental role in the MS Center’s growth as a world-leading MS-focused research program. We congratulate Dr. Vollmer on his upcoming retirement, and thank him for his many years of dedication to the Rocky Mountain MS Center and our MS community.

During his time here, Dr. Vollmer and the RMMSC at CU team pioneered an approach to treating MS that is focused on maximizing lifelong brain health. Their focus on early detection and efficacious treatment has played a role in changing the way MS is treated across the world, and helped lay the groundwork for recent advances and expansions in disease modifying therapies that are reshaping the landscape and outlook for today’s MS patients.

We recently sat down with Dr. Vollmer for a discussion about his career, his work at the MS Center, and his vision for the future.

InforMS: What first inspired you to go into the field of medicine and then into the field of neurology specifically?

Dr. Vollmer: As far back as I can remember, I was always interested in biology and zoology. When I started looking at careers, back in the early 1970s, there weren’t a whole lot of biologist and zoologist jobs around. I pursued medicine and it didn’t take very long to realize you’d ultimately have to pick an organ to specialize in. It seemed to me that dealing with the brain, the key organ that allows us to manifest what we think of as being human, was a more interesting focus and also the least understood organ.

However, when I did my undergraduate degree and then started medical school the field that I became attached to was the immunology system. As I began to think about how to develop a career, I began to look at ways to blend my interest in immunology with neurology. I had an Aunt who had MS when I was 12 years old and she died very young from it. Focusing on MS was a natural fit because in the 1960’s MS became a sub-specialty in neurology. We didn’t have any treatments for patients, but there was a strong research community focused on it, and at an academic level it was a career opportunity.

InforMS: Please tell us about the early days of your career.

Dr. Vollmer: I completed my undergraduate degree at the University of Wyoming, then completed medical school and residency at Stanford University. Stanford was a real hotbed for immunology and there were prominent leaders in the field of immunology. Larry Steinman was a pediatric neurologist who was finishing his residence three years ahead of me. He became one of the youngest faculty members and ultimately the youngest full professor at Stanford for his work on the immunology of MS. I completed a fellowship in his lab and worked there a few years in addition to doing my residency training. I was planning on following Larry’s path and pursuing more of a basic science career working in the lab full time.

When I finished my residency and fellowship training, I was recruited to go to Yale and given a start-up package that included a funded laboratory. At the same time, I set up a clinical practice that focused on MS, because we didn’t really know much about the rest of the inflammatory diseases we now treat. By 1989, we were beginning to think about clinical research in MS and that’s when the first in-human trials began for the interferons. I got involved with that early development of those agents, became part of an international community of MS specialists, and had the opportunity to travel around the world to collaborate with researchers.

It was kind of a heyday in MS research – it was the first time we had large clinical trials in MS with novel agents. That really attracted my attention and moved me into more patient care and patient related research and less animal related research. It was a revolution in our field. Just prior to that, it was a “diagnose and adios field”, we didn’t have much we could do about the disease. We would make the diagnosis and commiserate with the patients and try to treat them symptomatically. If they really were motivated, we would use agents we had available that didn’t work very well and were pretty toxic- chemotherapeutic agents and steroids. We would do our best, but we often ended up harming patients more than we helped them with the therapies.

Now MS is one of the most treatable diseases we see. Our ability to change the nature of this disease went from not much up to 1991, to moderate slowing with the interferons and glatiramer acetate, to where we are now such that if we can diagnose early and treat early, we can pretty much keep people from developing disability that essentially all of our patients developed prior to 2006.

InforMS: Could you please tell us more about what it was like to be a part of that revolution?

Dr. Vollmer: There were a lot of bright people working in basic science and clinical research related to MS around the world. Prior to the late 1980s and early 1990s, they were by-and-large working on their own. Then industry stepped in with large amounts of money to invest in this area. That focused the field’s attention on the interventional treatment side. Prior to that, there were a lot of good ideas, but most of them never made it into the clinic because they were done in university laboratories without the resources to do the pre-clinical work needed to do a human trial. The only human trials that had been done were pre-existing drugs that we used for other diseases.

MS is an example of what happens when a particular disease is identified by the pharmaceutical industry (pharma) as a potential profitable investment. That is due to the costs inherent in the human treatment trials which is in the hundreds of millions of dollars. It wasn’t as though the government wasn’t involved. Funding for these studies was blended between federal sources, foundation sources, and pharma. But pharma put in the bulk of the funding and they had the team of scientists, lawyers, writers and everything else necessary for the drug development process.

Clinicians and researchers collaborated with pharma to try to understand the disease better and to tailor their therapies and study designs to more relevant outcomes. That led to many vigorous collaborations with physicians and scientists from around the world both on pharma supported studies and investigator initiated studies funded through foundations and the NIH. This synergistic environment accelerated the development of new treatments for MS by encouraging many companies to invest in treatments for MS. Only about 20% succeeded, but that produced the 20 or so therapies we have now.

The community of physicians and scientists, including statisticians, ethicists, and experts in clinical trial design, really brought us all together to do many different projects. Along with Carolyn Schwartz, I created the North American Research Committee on Multiple Sclerosis (NARCOMS) which is a powerful patient registry that blossomed into many other registries to document outcomes and patient needs in a more effective way than had ever been done before.

As a result, MS has been one of the major successes in modern medicine in terms of rapid development of highly effective therapies for a disease previously thought to be untreatable. Unfortunately, this was part of a strategy by pharma to develop therapies for rare diseases and charge extraordinary amounts of money for them. The American system allowed them to do that. So it has had good effects in developing effective treatments for MS and enabling us to minimize disease activity while maximizing lifelong brain health. But it has also led to a crisis in healthcare: with many new and excellent drugs that society just can’t afford. By the way, recent studies suggest that this year (2021) is going to be the most profitable year for pharma ever.

InforMS: What are some of the most significant challenges facing clinical MS care today?

Dr. Vollmer: We are now one of the most interventional fields there is. We have excellent therapies and we are very focused on patient care. Therapeutics is now a major part of what we spend our days on. Developing a specialized comprehensive program has continued to be a major challenge for us because we are working within a very large health care system and trying to carve out special approaches to a certain class of diseases is difficult.

In the 1990’s I was part of a couple different systems where we actually did have dedicated staff with a dedicated physical space for our team members, so we were able to be much more a multi-disciplinary clinic. With the growth of medicine along these corporate lines, where we are now part of these large corporate systems, we have gone backwards a bit. Unfortunately, we are at a time now where we could really use a multi-disciplinary team even more than we could use them before. That means having physical therapists, social workers, occupational therapists, psychologists, nurses that are part of our care team in a stable way.

If anything, I would say American medicine is just as fractured now as it was 30 years ago. That’s why I think that our priority for the future should be to succeed in developing a multidisciplinary health care delivery system for MS that is designed to focus on a comprehensive care model that really can help patients maximize lifelong brain health.

For our young patients who we can treat at the beginning of the disease, many of them do fantastic. But many others won’t. And it’s because of co-morbidities, other health issues, and social issues that prevent them from reaping the full benefit of the therapies we have now. We must be able to provide long term support for healthy lifestyles, diet, recovery of function, and social consequences of disability. We can make a major change in what happens to people in a way that not only benefits them, but benefits society by decreasing health care costs and decreasing the burden of disease.

InforMS: What drew you in 2008 to come here to the University of Colorado and the Rocky Mountain MS Center?

Dr. Vollmer: University of Colorado’s School of Medicine had really evolved to one of the better schools in the country and I think in the world. Part of that had to do with the development of the Anschutz campus which really led to a major shift in hospital administration and a huge focus on patient care. The hospital and the university were supporting clinicians and clinician scientists who were focused on human disease and the human model of disease in ways a lot of other schools were not.

When the opportunity to partner with the Rocky Mountain MS Center came up, I recognized that there was a synergy there. The Rocky Mountain MS Center had a history of education programs, patient support programs, philanthropy to support patient care, and a real focus from a community standpoint on MS patients and families dealing with this disease.

Being able to take an academic position at the University of Colorado and still be involved with Rocky Mountain MS Center led to opportunities for things I’d always wanted to do but couldn’t do with other MS Centers. It’s very hard when you have a program that is really built around clinical science funding and patient care to expand that into patient education. The Rocky Mountain MS Center had the staff and team to do just that.

Adding the skill sets of the Rocky Mountain MS Center onto an academic clinical program focused on MS and other related diseases, gave us a much better visibility and a much broader reach. We became regional rather than city-based. And it significantly improved our ability to educate and empower patients and families around the country. In clinic visits, you’ve got 30 minutes, so you are limited in what you can do. But the Rocky Mountain MS Center’s ability to put on education and outreach programs allowed us to constantly get the message out in a big way. That work not only impacted patients, but it impacted the clinicians involved in patient care too.

Also, the field of MS has been moving in this direction where we were losing sight of the other inflammatory diseases of the central nervous system – Acute Disseminated Encephalomyelitis, Neuro Myelitis Optica, autoimmune encephalitis, and other inflammatory neurological diseases. Throughout my career, I always dealt with all these unusual and rare inflammatory conditions of the nervous system. I was able to broaden the RMMSC program as a center for the care of individuals with rare inflammatory diseases of the nervous system in addition to MS.

Dr. Corboy and I have often talked about the fact that we’ve been involved in medicine for a long time, but the rapid growth of the program at the University of Colorado and UCHealth since joining with the Rocky Mountain MS Center in 2008 has been remarkable and not something we had really seen in programs before. We went from one of the many MS clinics that existed in the United States to one of the top three or four in a relatively short period of time.

The collaboration between the Rocky Mountain MS Center, University of Colorado, and University of Colorado Hospital has led to a strong foundation for us to be able to positively impact other rare inflammatory diseases that we see, as well as MS. I think ultimately the partnership will prove to be as beneficial to those diseases as our ability to impact MS.

InforMS: You have been at the helm of so much cutting edge, pioneering research. Can you talk about the research you’ve been most involved in, what the research has accomplished, and the future direction of the research that you’ve laid such a strong foundation for?

Dr. Vollmer: One major focus was trying to identify astrocytes as another therapeutic target in MS and related diseases. Another has been using the animal model to understand better the actual mechanism of action of the drugs that are approved to treat MS. It’s an unexpected reality that we have very poor understanding of the mechanism of action of the vast majority of drugs developed for human use at the time they are being developed. The reason for that is pharmaceutical companies often go into human trials long before they really know the basic biology of any given agent. They tend to learn about how the drugs actually work in humans after the fact.

But that mechanism of action information is really key. It’s critical to understand how the drugs really work and how they really help MS. That information might give you insights into additional strategies you can use to improve in terms of decreasing risk and improving efficacy. I was interested in figuring out how we can learn from the successes we had in the human model to better understand the true biology of MS, and then taking that information and thinking about the next generation of therapies.

I had the advantage that there is a tremendous amount of research going on in the field of immunology and MS. Having access to this resource allows me to look for snippets of information that help me better understand what was going on in the human model. And that’s where the concept that astrocytes in the human disease were actually a key player came from. I will continue to push the field to recognize astrocytes as a potential therapeutic target and to help them understand some of the therapies we already have are already working through astrocytes.

The other area is trying to change human disease from simply a therapeutic target into the model that we use for research. That’s why I focused on building the Rocky Mountain Translational Neurology Research Lab – the biomarker lab. If you want to understand the biology of human disease, you need the ability to study the disease without causing harm. The Rocky Mountain Translational Neurology Research Lab has given us the ability to dissect the biology of MS and related diseases by monitoring very rare molecules in the blood that are being released from the brain as a result of the inflammation. We can study different cell populations in the brain by seeing what molecules from them are being released into the blood. We can also see the consequences of therapeutic intervention.

I also spent a lot of time on clinical trial design from the late 1990’s up until now. I focused on identifying study designs that were friendlier to the study participants. I also aimed to use outcome measures that were more relevant to the disease. Open label designs, where you’re not randomizing people and you’re not using placebo, but instead you are studying what happens in people as they are normally treated is a valid study design. Randomized placebo controlled trials are very powerful because you can control for many variables and you can do the study with smaller number of patients in shorter period of time. But, what it means is that if you have a therapy that you know has some benefit to MS patients and you’re denying the placebo group that treatment, then the placebo arm is going to incur injury that was preventable.

It took a long time to get them to move to study designs where you didn’t use a placebo, but instead used one of the other approved drugs. But even there we know that the drugs we used as the control arm are less effective than other treatment options. There is a price that is paid by participants in those trials. Therefore, I strongly believe that in therapies where we already know there is efficacy, those should be open label active treatment trials. The key question for us now is not about finding new therapies; it’s about determining which of the current therapies provide the best treatment options for our patients to minimize the risk of the disease and also to minimize the risk of the therapy.

Also, we don’t have curative therapies. The primary focus of therapy development should be on therapies that terminate the inflammatory attack on the brain, and on therapies that are reparative and help patients restore function. Those are the two big needs we have right now.

InforMS: What gives you the most hope?

Dr. Vollmer: I’ve been talking about the concept of neurological reserve and brain health since I first started working with Dr. Carolyn Schwarz in 1993 with the Rocky Mountain MS Center. Together with the team at Rocky Mountain MS Center, we have advocated for early treatment with highly effective DMTs to improve long term outcomes, a practice that has now been confirmed by multiple studies as the best approach to managing MS. At the Consortium of MS Centers Annual

Conference this fall, a number of papers were presented about how early intervention with high efficacy therapies have far superior results than the traditional escalation approach. And that’s been paralleled in the literature with a number of papers published– at least eight papers in the last year – from databases, randomized trials, the Swedes’ experience, and from our experience. The concept of early interventional with high efficacy therapies is now moving fairly rapidly throughout the world, and I think it will become the standard throughout the world in the next couple of years. If we can get the world to adopt this strategy, we can take MS from a disease where most people will have some significant disability at least to a disease where most people won’t have any disability and can live normal lives.

The other area that gives me hope are efforts in using real world data to continue to improve therapies and decrease the risk profiles. We have highly effective therapies, but the reality is that some patients are going to develop significant risks with the use of those therapies primarily with the suppression of the immune system. As you know, with the COVID-19 pandemic, we have gone through multiple iterations of how we approach patients to fine-tune therapies to minimize risk of COVID. In one of the most recent papers, they looked at 1,400 patients on all of the MS therapies and compared them to what was known in the datasets about non-MS patients who contracted COVID. It doesn’t appear that the MS therapies had any major impact on COVID outcomes, which is reassuring. I see ongoing opportunities to improve patient experience, decrease risk, and improve efficacy.

The growing technology to allow us to dissect the human model also gives me hope. We started in the 1990s with the MRI and that was incredibly powerful because you could look at the anatomical changes that occurred in the disease. But the imaging is still a pretty limited and crude instrument to use when you are trying to dissect regulatory systems in the brain and the immune system. The development of the Simoa technology that we now have in our Translational Research Lab was the next major breakthrough. And the power of molecular biology and genetics continues to be tremendous. The ability to take a few cells from an individual and use those cells to really understand how the body is communicating with all the different systems within is remarkable.

InforMS: What will retirement look like for you? What are your plans and what are you looking forward to?

Dr. Vollmer: As you go through life, particularly when you’ve had a great career, in an area that was absorbing, it becomes all consuming. You sort of lose connection with a lot of the other things that bring joy to life – taking a walk, going on a hike, spending time with family, enjoying music, going to the theater, and traveling. There’s so much to do in the field with so many great opportunities you get more and more absorbed in it because there are more and more good things for you to do. Those opportunities might turn into significant advances in the field and they demand your attention. Our group has grown and we have a lot of great people involved in our team. They can take the ball and run with opportunities.

However, there are a few areas that I’ll continue to engage in: advancing the concept of neurological reserve, astrocyte research, and improving clinical trial design. Now, I will have that time to focus on one very specific question, search the world’s literature to see what we know about that question, and put together a review article to help push the field forward. Review articles are very important for us because we can synthesize what’s known and pose the key questions. That work can inform young investigators to move research forward and advance the field. So, that seems like an appropriate role for an ‘old guy’ like me (Laughter).

InforMS: What’s the message that you would like every person who has been newly diagnosed to hear?

Dr. Vollmer: MS is now one of the most treatable diseases that we see in neurology and there are many options that can be explored. They have the opportunity to pursue highly effective therapies that really can prevent them from having the problems that our patients heretofore have had. This isn’t a disease that should alter their lifestyle in any significant way. It doesn’t have to fundamentally change their ambitions, their plans for their family, or any other goals that they have.
The collaboration between the Rocky Mountain MS Center, CU and UCH has a great future going forward. We live in a world with a fair number of tragedies that can affect us and our neighbors which can include a diagnosis of one of the diseases we treat. The support services and education programs that the Rocky Mountain MS Center provides are critical to help individuals and families navigate those challenges. Our collaboration allows us to have a greater impact on the lives of individuals and families as we work together.

InforMS: We are so appreciative for all of your tremendous service, dedication, and commitment and the impact you’ve had on the field of MS research and countless individuals and families throughout your career. Thank you!

Dr. Vollmer: The other major benefit of the early decision I made to go into the field of neuroimmunology and MS is that it led to an incredible opportunity to work with wonderful people.

Throughout my entire career, I’ve been surrounded by bright, intelligent, and ethical human beings who are committed to a cause and committed to service to mankind. I am profoundly grateful.

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