ACT-CMT opened its doors and windows and basically said, “Alright, everyone with CMT1A, come on in.” With an open call for another 100 participants, the largest-ever CMT1A Natural History and Biomarkers study is now becoming the largest-est most biggest-est ever, and honestly, at this point, the study has gotten so big that language is tapping out.
Understanding how CMT1A changes over time is one of the biggest challenges in developing treatments. Unlike diseases that progress rapidly, CMT1A moves slowly, which makes it hard to know whether a potential therapy is creating real change or whether the disease is simply following its usual course. The Accelerate Clinical Trials in CMT (ACT-CMT) study, supported by $1.2M from CMTA, is designed to answer this question with clarity.
Led by David Herrmann, MBBCh, at the University of Rochester, ACT-CMT brings together a global group of CMTA Centers of Excellence. Joining Dr. Herrmann’s Rochester, NY clinic are Steven S. Scherer, MD, PhD, at Penn in Philadelphia, Reza Seyedsadjadi, MD (“Dr. Reza”), at Massachusetts General Hospital in Boston, Michael Shy, MD, at the University of Iowa in Iowa City, Davide Pareyson, MD, at Besta Neurological Institute in Milan, Italy, and Mary Reilly, MD, MBE, at University College London, UK. Each doctor uses the same set of assessments in the same way, allowing researchers to follow individuals with CMT1A over many years and identify the patterns that matter for future clinical trials. Further support for the study is provided by Joshua Burns, PhD, at St. Jude in Memphis and Gabrielle Donlevy, PhD, at the University of Sydney, through data analysis, quality assurance, and training.
“ACT-CMT was designed to answer one of the hardest questions in CMT1A research: how the disease changes over time,” said Dr. Herrmann. “By extending the study, we can follow people longer, collect deeper clinical and biological data, and build the benchmarks future clinical trials will depend on. Initial findings from this extended phase are expected in 2026, and they will help guide how upcoming trials are designed and evaluated.”
“When I received the phone call from CMTA’s London Center of Excellence inviting me to participate in the ACT-CMT study, CMTA’s research became personal in a new way,” said Katherine Forsey, PhD, CMTA’s Chief Research Officer. “The visit was well organized, involved a lot of physical assessments and questionnaires, and I found it genuinely interesting. As a patient living with CMT1A, being part of a study that may help shape future clinical trials means a great deal to me, and I look forward to returning next year to see how my CMT has progressed.”
ACT-CMT also collects blood and skin samples from some participants. These samples are added to a growing library of biological information that may reveal early signs of meaningful change. At the University of Wisconsin, John Svaren, PhD, is using a new technique to measure the levels of two important myelin proteins, PMP22 and MPZ, in blood samples. This work may ultimately lead to practical biomarkers that enable us to monitor the effects of any future CMT treatments using a simple blood test.
A Long Look at CMT1A
The strength of ACT-CMT comes from time. Participants in the original phase of the study are now returning for their fourth and fifth annual follow-up visits. These return visits create a detailed timeline of how CMT1A progresses, helping to clarify which changes are consistent across the subtype and which vary from person to person.
To build an even fuller picture, the study has now expanded to welcome 100 additional individuals with CMT1A. This broader group introduces more variation, comparisons, and real-world differences that help researchers understand how CMT1A behaves across a wider range of individuals.
During each visit, participants complete a full set of clinical assessments and provide blood and skin biopsy samples. Together, these data points give scientists two types of information. The clinical assessments show what is changing. The biological samples help explain why those changes are happening. Both are essential for designing trials that can detect real improvement in the shortest amount of time.
Why This Work Matters
Before treatments can move into clinical testing, researchers need a reliable picture of how CMT1A progresses and a set of measurable signs that show whether a therapy is making a difference. ACT-CMT is building these tools. The long-term follow-up data provide a clear picture of the disease. The biological samples help identify potential biomarkers that may confirm the effects of a potential treatment.
ACT-CMT is more than a long-term study. It is the foundation that will help future trials succeed. Each visit, each sample, and each new participant brings us closer to treatments and, ultimately, a cure.
ACT-CMT Needs You
If you have CMT1A and want to be part of the largest CMT natural history study, ACT-CMT is the study for you. Bring your curiosity and yourself. Doors and windows are open. There’s a spot with your name on it, if you meet the eligibility criteria. Additionally, if you are an adult without CMT or risk factors for peripheral neuropathy, you can also participate through our University of Rochester, University of Iowa, and Penn Centers and serve as a control participant for the study.
