By Emily Leclerc | Waisman Science Writer
Waisman investigator John Svaren, PhD, professor of comparative biosciences, was recently named the interim associate vice chancellor for biological sciences in the Office of the Vice Chancellor for Research and Graduate Education (OVCRGE). We sat down and learned a little bit more about him and the research that he conducts at Waisman. (Answers have been lightly edited for length and clarity.)
Congratulations on your new role! Would you like to talk a little bit about it?
It is going to be an interesting challenge. This campus tries as much as possible to support labs, has different ways to provide bridge funding, and has other kinds of funding to support researchers in their ability to carry out research and obtain new grants. In this position, I’ll be working to direct some grant and internal grant processes, help with reviews of those, and administer them.
I think I was a little bit surprised to get the phone call but I’ve been grateful for all the support I’ve received over the years from UW-Madison and if I can help to extend that to other people over the next year or so, then I’m happy to do so. I’m looking forward to it.
Would you like to tell us little bit about yourself and what you do at the Waisman Center?
I’ve been here at UW-Madison since 2000. I’m part of the School of Veterinary Medicine where I do most of my teaching, but my lab is at the Waisman Center. I was invited to move my lab over to Waisman in 2007 and since then I’ve gotten involved in the center’s core grant, which has been a mainstay of the center for many years. I serve as the Intellectual and Developmental Disabilities Models Core director, as well. It has been a real pleasure to be part of the Waisman Center. Scientifically, my lab is focused on cells that make myelin in the body, both in the brain and the peripheral nervous system. We’re interested in diseases that affect those cells.
Can you explain what myelin is?
Myelin is a layer of mostly lipids or fats that wraps around the projections or axons of nerves. These axons carry the nerve impulses from your spine to your muscles. The axons can be very long and vulnerable since they are a single cell that goes from your spinal cord all the way down to the muscle of your big toe. So, in order to protect themselves, they are wrapped by this sort of lipid-rich or fatty layer of myelin. Myelin is made by cells called Schwann cells in the peripheral nervous system – which includes any nerve that leaves the spinal cord and goes out to your skin or muscles.
Your lab does quite a bit of work on Charcot-Marie-Tooth disease (CMT) because it is a disease that affects the myelin on nerves. Can you tell us a little bit about CMT?
CMT is a neurodegenerative disease that affects peripheral nerves. Some of the condition’s effects are similar to muscular dystrophy and in fact, some research in the CMT field has been funded by the Muscular Dystrophy Association. Your nerves are really important to make your muscles strong and to move wherever you want them to. And in the absence of healthy nerves, that ability to do so really deteriorates over time. People with CMT have progressive neuropathy – or nerve damage – that predominantly affects the hands and feet, the longest nerves of the body. It can be painful. It involves muscle weakness, smaller muscles, and decreased sensation. There are some foot curvature issues that oftentimes require surgery. It causes fatigue, and overall muscle weakness as it progresses. It’s a disease that is relatively common for rare diseases. As of today, there’s no effective treatment for it.
What kind of research have you and your lab done on CMT?
We got into this by studying cells that make myelin around nerves. In the peripheral nervous system those cells are called Schwann cells. We were interested in the genetics of that and how the genes get turned on and turned off. Then we realized that some of our research was related to CMT. In fact, some of the genes we were studying are mutated in different forms of CMT. So over time, we realized that we could target our research in this direction and we did a variety of different things. For a while we were heavily involved in trying to set up screens for new drugs for CMT. We’ve been looking at new ways to treat the most common form of CMT, which means manipulating gene levels of a critical gene. And then, over time, I’ve gotten more involved with other clinicians in this network of neurologists that work on CMT. Lately, we’ve been doing a lot of what we call biomarker work. This is a way where you can take blood samples or skin samples, and determine if there’s a way you can measure something that’s relevant to CMT, and then, ideally, include that in clinical trial design.
What CMT research are you and your lab currently working on?
We have a variety of different projects going on. As I mentioned, we have a major biomarker project that we’re working on and really trying to get prepared for potential clinical trials. We also have a recent grant that we got to continue our work on how Schwann cells are really important after nerve injury. We’re interested in all the things that Schwann cells do after nerve injury to foster the regeneration of nerves. Schwann cells do amazing things to support regeneration of nerves and we’re interested in how that’s controlled and how that is carried out. So that’s really a major project. And like I talked about earlier, myelin is made out of a fatty, lipid-rich substance and it turns out the metabolism of the Schwann cells is really important. It has to generate a lot of this lipid and fat so we have another project that’s looking at the metabolism of how all this myelin lipid is made, which appears to be impaired in CMT.
You talked about how your CMT biomarker work is geared particularly towards being used in clinical trials. How could this work be utilized in a potential clinical trial?
CMT is a slowly progressive disease in contrast to ALS, which affects the same neurons in the peripheral nervous system. ALS, once it occurs, progresses very quickly but CMT is much slower. What we really need to support a clinical trial are things that you can measure at specific times after you’ve started a therapy. In a clinical trial, in order to show that you’re actually having some success, you need something measurable. That can be hard to find in a slowly progressive condition.
For our work, we realized that there’s a key gene that’s involved in the major form of CMT. We found ways we can measure that key gene in the skin using a special kind of technology. What this would allow you to do is – even within a month or so of starting a clinical trial – see if that key gene has been changed by the drug the way we hope it would be. This would be confirmation that the key gene has been changed. It would give you confidence that a longer clinical trial will actually be successful. There are other biomarkers that we’re measuring in blood and we hope that these would respond to treatment in the early phases of a clinical trial. And if they change then that would support the extension of the clinical trial to longer times. Because sometimes it might take a while for patients to really notice that their symptoms are changing.
Are there any CMT clinical trials on the horizon?
Possibly. One of the exciting developments in our field is that there was a company that developed a therapy that allows you to modulate this key gene. This was a company called Dtx Pharma. This company had gotten to the point where they were poised to start clinical trials and hoping to start in the next year or so. Well, because of the success of their technology, they were acquired by a major pharma company called Novartis.
We’re hoping and anticipating that Novartis will try to start these clinical trials on a similar timeline. We don’t know any specifics yet, but we’re hoping for 2024. We think there’ll be some other trials as well. I work with a lot of clinicians who are working on other kinds of things that you need for clinical trials. And we’ve been sort of integrating and coordinating our efforts to really have a package of things that will make companies better able to design a more efficient clinical trial.
If Novartis decides to proceed with a clinical trial, would your biomarker work be used in its design?
We anticipate that our assays, particularly the skin assay I was telling you about, would actually be a key measure in it. Because one of the ways that we have to modulate this key gene is to bring it down. But if it’s brought down too much, it could have some side effects. So, one of the things our technology can do is to try to make sure that we’re lowering it into healthy range and not lowering it too much. We anticipate that this would be used in that clinical trial. But that has not been confirmed and we have no information on the trial yet either.
I know that you are also very involved in the CMT community. Can you talk a little bit about that?
Over time, with our research, I became part of the board of the CMT Association. This is the largest organization in the United States that’s focused on CMT research. I also have become chair of its scientific advisory board. And as such, I work with researchers who develop research proposals for funding. I also interact with companies that are interested in investing in therapy development for CMT. As an organization, we try to provide resources and information to help companies learn more about the disease and what they would need to do to get to clinical trials. In addition, it does also have a large network of individuals affected by the disease. I speak at patient groups and meet with individuals/families affected by CMT. In fact, even on Thursday, this week, I have a teleconference with a group in St. Louis to give research updates about things that are in process and try to answer questions. I’m not a neurologist, but over time, I’ve learned a fair bit. So, I can’t always answer everyone’s questions, but I try to do the best I can.
Moving forward from research, I am curious what your favorite part about being a researcher at the Waisman Center is.
The people in the center are really amazing. We have some really spectacular scientists and we work together in many different ways. We work on projects and the core resources in order to support researchers in the center. We’ve always had great leadership in our center. I think too that people are really motivated by interacting with individuals who have the conditions that we work on. Across the board, I think that’s definitely the case. Certainly, the diversity of things that happen in the center is amazing. You have brain imaging and people that work on hearing or speech perception, and so it’s a place that you can actually learn about things that are not just in your own field. So, there’s really an amazing diversity of things here, which I enjoy.
When you are not in the lab working on research, what types of things do you enjoy doing in your spare time?
I enjoy swimming, usually a few times a week. Sometimes my daughter will do it with me, which is fun. I enjoy biking. I bike to work. When I have enough time, I enjoy reading. But sometimes I don’t have as much time for that as I would like to.
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Learn more about the Waisman Center's 50th Anniversary, including events, history, stories and images: 50 Years | 1973 - 2023 |