Skip to main content
Inherited Neuropathy Consortium logo

Consortium Spotlight: Advancing Discoveries in Charcot-Marie-Tooth Disease

August 9, 2022

The Inherited Neuropathy Consortium (INC) is a group of academic medical centers, patient advocacy organizations, and clinical research resources dedicated to conducting clinical research in Charcot-Marie-Tooth disease, a group of disorders that affect the peripheral nerves. Here, program manager Shawna Feely, MS, LGC, and principal investigator Michael Shy, MD, share the history of the consortium, current research, and future plans.

What are the overall goals of the INC?

Charcot-Marie-Tooth disease (CMT) is a rare disorder with over 100 different genetic causes and multiple subtypes. This genetic condition causes peripheral nerve dysfunction, leading to progressive disability in patients of all ages. Progress has been made to provide a genetic diagnosis to most families with CMT, allowing for the development of potential treatment trials. However, there are many people with this rare disease where a genetic diagnosis cannot be made, and that may limit treatment options in the future.

The goals of the INC are to use current technology—such as whole-genome sequencing (WGS)—to identify novel causes of CMT; to develop various outcome measures across the lifespan of a patient (infants to adults) in preparation for treatment trials; and to help lead the way for treatment trials as they become available for different forms of CMT.

How did the INC team come together, and how did you become a part of the RDCRN?

Prior to being part of the RDCRN, we collaborated with a small network of sites that had an interest and expertise in CMT. These investigators saw the potential for improved ability on how to evaluate a patient with CMT and the limitations in providing a genetic diagnosis at the time, as well as the necessity to improve both of these for clinical trial readiness.

By becoming part of the RDCRN, we had the ability to create a larger infrastructure in which outcome measures could be created and validated, support for research-based testing such as WGS and identification of biomarkers was possible, and the enrollment of more patients with this rare disease across a larger network was obtainable. This enabled the INC to help discover genes for CMT, identify methods to evaluate patients in a standard way across the entire lifetime, and start treatment trials for inherited neuropathy.

Can you tell us more about the rare diseases you study?

CMT is a debilitating neuromuscular disease caused by peripheral nerve dysfunction that can lead to progressive weakness and sensory loss in all four extremities. CMT can also lead to structural changes in the feet and hands, difficulties with gait and balance (to the point where aids are often required), and sometimes other system involvement.

Collectively, there are over 100 different genetic causes of CMT, which makes diagnosis often challenging—especially as not all genetic causes are known. This is often a slowly progressive disorder, which can make it challenging to identify change over time. Currently, no known cures exist. We evaluate patients who have or are at risk for all forms of CMT, and they are provided the option to participate in multiple clinical trials through the INC depending on the type of CMT they have, age, and other factors.

What are your current research projects?

How has your research impacted patients?

Currently, there is no cure for any form of CMT. However, genetic identification and diagnosis is an essential first step to the potential for a cure. Through our gene discovery program for CMT, the INC has helped to identify half of the genes currently known to cause various forms of CMT. This not only has allowed families to have answers and options that they did not before, but has also led to treatment trials, such as one currently starting for SORD-Neuropathy.

In addition, the development of outcome measures has allowed patients and families to have a better understanding of disease progression over time and what to expect in their future. As we have seen, this translational approach has not only had a direct impact on families, but has also brought us closer to a cure for forms of CMT—which is the ultimate goal for this population.

What new research directions or goals are you pursuing?

We will continue with gene discovery and validation of a variety of measures for CMT. However, moving beyond this is an important next step to treatment trials. Due to our participation with the RDCRN, we are ready to take this step, which will require partnerships outside of the INC.

We will continue to provide care for patients with all forms of CMT and continue the development of ways to measure change over time. However, we are now at the stage of clinical trial readiness where treatment trials are beginning. This is exciting for the INC and the entire CMT population.

How do you envision that the diseases you study can ultimately be cured?

Although CMT is rare and complex—as there are many different genetic causes—by definition, it is a genetic disease. Therefore, the biological basis for the disease can be identified. With gene identification, the mechanism of disease can be understood. Through various forms of gene therapy approaches or by understanding the disease mechanism and providing an intervention that prevents functional loss—as in the case with SORD-Neuropathy—cures for CMT are in the future. By working with the RDCRN, we have been able to move closer to this goal, which will be highly impactful for all of those affected by CMT.

The Inherited Neuropathy Consortium (INC) is part of the Rare Diseases Clinical Research Network (RDCRN), which is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Division of Rare Diseases Research Innovation (DRDRI). INC is funded under grant number U54NS065712 as a collaboration between NCATS and the National Institute of Neurological Disorders and Stroke (NINDS).

View News by Topic

Recent Articles

FacebookTwitter ShareLinkedIn ShareEmail Share