A scientist’s perspective on the landscape of CMT research

Without direct ties to the research community, it’s easy for a patient to feel disconnected from the researchers who work to better understand Charcot-Marie-Tooth disease (CMT) in hopes of finding more treatments or a cure.

A few weeks ago, in an attempt to learn more about CMT research, I spoke with John Svaren, PhD, a professor of comparative biosciences at the University of Wisconsin-Madison and chair of the Charcot-Marie-Tooth Association’s (CMTA) Scientific Advisory Board. Excerpts of our conversation follow.

YL: How did you first get involved in CMT research?

JS: My exposure to neuroscience was limited in my training, but my first exposure was around 1997 or 1998, when we were studying a particular gene that someone found to be the cause of a very severe form of CMT. So that changed my focus.

I was more of a biochemist or molecular biologist, but I always had an idea to work on something with a medical application, and I saw this as an opportunity.

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Can you share how the CMTA’s Strategy To Accelerate Research, or STAR initiative, and similar initiatives have changed the landscape of CMT research?

When I first got into CMT research, the most prominent activity was identifying new genes. With the STAR initiative and similar efforts, we really started thinking about how to move from knowing about the genes [that cause CMT] to developing new therapy types.

About that time, we also created resources for companies, including an animal model testing program where we had models of different forms of CMT available to companies that wanted to test molecules to see if they might be efficacious in animal models of the disease.

We also broadened the way we design clinical trials. One of the limitations of CMT is that it is a slowly progressing disease. And that’s good [for people with CMT], but it’s bad in clinical trial design because if someone is slowly progressing, even if they get the perfect treatment, you won’t know for a while that they’ve stabilized or got a little bit better.

We realized at the time that we really needed to improve our clinical trial design, because most companies will not invest in supporting a clinical trial that’s going to take two to three years. Companies expect a faster indication that [a potential treatment] is going to work.

Can you talk a little about the STAR Advisory Board?

On our board, we have clinicians, scientists, and people who have pharmaceutical company experience. We have a grant program resources to help companies working to help people with CMT. But with grants, we really try to award them when we see a viable pipeline to a clinical trial.

From a scientific perspective, we can often say, “This has merit because we understand certain aspects of a disease.” But sometimes you need a clinician who understands the potential clinical application and someone from pharma who can say, “This is something that can be developed and has precedent in the field.” We have [an interdisciplinary board] because no single person has all the perspectives.

What are some important aspects of CMT research that may not get enough coverage?

In many cases, there is broader relevance to projects than what one may initially focus on — just one subtype of CMT, for example. There are often opportunities to expand the scope later on. The NMD Pharma clinical trial [evaluating ignaseclant, formerly known as NMD670] is an example. We also often find potential common denominators [across multiple subtypes of CMT], and we always try to exploit those as much as possible.

An additional notable challenge is that whatever treatment we come up with may be a lifelong treatment. As such, there are additional precautions required to ensure a treatment is safe.

[In terms of bottlenecks] the whole field of pharmaceutical development goes in cycles, and we’re in a down cycle now. In fact, the overall investment in biotech has waned a bit. The federal funding environment is a limitation as well right now. Foundations and companies can’t fund everything.

What can CMT community members do to support researchers?

Awareness and providing support mean a lot. We do have ongoing work to develop patient history and biomarkers, and participation in such trials is really important.

Taking advantage of shared resources and thinking of the whole CMT community as an entity that together can have more power — to write congresspeople, for example — may also help.

Note: Charcot-Marie-Tooth News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Charcot-Marie-Tooth News or its parent company, Bionews, and are intended to spark discussion about issues pertaining to Charcot-Marie-Tooth.