Examining Charcot-Marie-Tooth with Florian Thomas, MD, and Adrian Hepner, MD

While the nerve disease is not life threatening, patients may experience considerable poor quality of life and emotional distress.

Charcot-Marie-Tooth disease is a debilitating peripheral nerve condition affecting roughly 130,000 individuals in the United States. The disease has no cure, but specialists and non-specialists can work together to improve quality of life outcomes for affected patients.

In this month’s episode of The Rare Disease Report, Florian Thomas, MD, of Hackensack University Medical Center & Hackensack Meridian School of Medicine, and Adrian Hepner, MD, Chief Medical Officer of Pharnext, explained CMT, how it may be managed by care teams, and a therapy that could be on the horizon.

They emphasized the importance of increasing awareness and advocacy, noting that patients themselves may benefit from both continuous education and a combined team effort across specialties.

Below is the full episode, including highlights from the conversation.

HCPLive: What is Charcot-Marie-Tooth Disease?

Thomas: It is a condition of the peripheral nervous system, which involves the connections between the spinal cord and the brain stem and the muscles, skin, and internal organs. The symptoms and signs of Charcot-Marie-Tooth Disease include weakness, numbness, tingling, loss of muscle bulk, foot drop, and difficulty picking up things.

The condition starts, at a scientific level, in childhood. We are born with it if we have it. The manifestation onset varies between people — between childhood, young adulthood, even older adulthood.

It leads to disability because of foot drop, and people have a risk of falling. The condition does not really affect life expectancy, but it leads people to retire a couple of years early. Progression may speed up after age 50.

Can you elaborate further on the patient quality of life?

Thomas: As this is a lifelong illness, I take care of generations of patients. I care for 1 family with 4 generations, and I’ve followed some of the family members over 20 years. So, they have aged as I have aged.

One needs to be attentive to their changing needs. A teenager may be concerned about going on a blind date and stumbling as he or she approaches a friend. An older person may be afraid of a fracture when they fall. The manifestations are manifold, and so it takes a team to take care of patients well.

The schoolteacher needs to be able to accommodate a child that may not be able to run as well in school sports. It involves a physiatrist, rehab therapists who can help with ankle braces, house psychologists, and, also certainly, the primary care doctor.

It is important these patients engage in healthy living and don’t accumulate other conditions that can affect their nerves, such as diabetes. It is also important that they maintain an ideal body weight so that they are not at higher risk of falling.

You mentioned this can be a lifelong condition. What do the screening and diagnostic practices look like for these patients?

Thomas: Many nonexperts are unaware of the condition, and it may take years for the person to be diagnosed.

On the other hand, if a person is part of a larger family with CMT, the parent may be the first person to diagnose it — especially if the parent has CMT.

I take care of a woman who is now in her 70s who can diagnose CMT in her great-grandchildren at age 3. She sees how their feet hang down and their foot drops, and so forth.

It may be schoolteachers who alert the parents that their child falls a lot.

When we see a patient, to some degree and quite often, we can make the diagnosis at first glance. If we see very skinny calves, if we see foot deformities, toe deformities, it can be a first glance diagnosis.

In other people, it is much more difficult, especially if a person presents in later adulthood. One has to consider what else can be going on.

Currently, there are no treatments approved for this disease. How are these patients typically managed?

Thomas: I am glad to be part of a treatment team that involves rehab therapists, physiatrists, child neurologists, foot and ankle surgeons, podiatrists, and people whose expertise is in designing ankle braces that can stabilize a dropped foot.

I typically explore with the patients what is their main concern, and I try to address that over the course of time.

If there are other conditions I’ve identified, such as vitamin deficiencies, or toxic vitamin levels, or medications that can damage nerves, then we need to address those.

It’s unfortunate when patients are told that there is nothing that can be done for them, because we can certainly help them walk more safely, and we can equip them with tools that will help them close buttons, zippers, use tools, to make them function better in every day life.

You are involved in research surrounding a potential new treatment option for this disease. Can you explain that?

Hepner: We have done multiple studies on the combination of 3 existing drugs— baclofen, naltrexone and sorbitol—in relatively low doses compared to the currently approved doses.

We’ve tested this in a Phase 2 study, as well as a prior Phase 3 study that had some minimal, but not insignificant, issues in the formulations. Because of that, the study was interrupted early and it was not totally possible to interpret the results.

And so, we went back, we fixed the issue in the product, and we are now running a brand new study — a large Phase 3 study in 10 countries, including the United States.

Based on the data we’ve seen so far, in the prior blinded studies, and also in an open-label extension study, many patients stopped their decline and some patients improved over the status they had at baseline.

We believe, and we hope, that this ongoing study is going to replicate in a robust manner these results.

Do you have any advice or additional thoughts you would like to offer to clinicians or primary care providers about this disease?

Hepner: The patients that understand the disease are going to be the first and most important communicators helping other patients. This is a rare disease—but not so rare. At the end of the day, it is one of the least rare diseases. There are thousands of patients in the United States, the same in Europe.

One thing is to disseminate the data, share with colleagues, and let people understand that hopefully there is a treatment, but also there are many things physicians can do today.

Thomas: Once there is a medication that is available that patients are much more educated about than their CMT-specialist doctors, they will demand treatment. They will demand to get orthotic devices and foot and ankle surgery.

Having a medication for CMT will dramatically increase recognition of patients by doctors, reduce the time to a diagnose in a given patient from what can be 5 years to 6 months, make it more likely that the offspring of patients who also have the disease will be treated, and improve outcomes because of earlier recognition.

[Quotations edited for clarity.]

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