For people with CMT1A and CMT1E, timing could mean everything. CMT progresses slowly over time, and a treatment may have a different effect depending on when it begins. CMTA is investing $165,000 in a new study led by Michael Shy, MD, and Robert Piper, PhD, at the University of Iowa to find out when treatment could have the greatest effect in CMT1A and CMT1E. Their team will also study how much the underlying biology needs to change to improve symptoms and how researchers can tell for sure whether a medicine is working.
This project builds on more than four years of work by Drs. Shy and Piper studying CMT and myelin biology, including how changes in PMP22 affect peripheral nerves. This work laid the foundation for the questions they are now trying to answer.
The duplicity of PMP22
CMT1A and CMT1E are both linked to PMP22, a gene that helps peripheral nerves build and maintain their myelin. Myelin is the protective covering around nerves that helps them carry signals.
People with CMT1A have an extra copy of PMP22, causing the body to make too much PMP22 protein. CMT1E is caused by mutations in the same gene, and its effects can vary widely. In a recent study, Drs. Shy and Piper found that CMT1E progresses fastest during childhood and adolescence and that the specific mutation can affect its severity.
Although the genetic changes differ, treatments for both types may need to correct PMP22 activity without going too far in either direction. Too much PMP22 leads to CMT1A, while too little leads to the CMT subtype called HNPP. Researchers need to determine how much PMP22 levels can change and strike the right balance.
Finding the right treatment window
Drs. Shy and Piper will develop laboratory models to study whether the timing of treatment changes how CMT1A and CMT1E respond.
The models will help answer three questions that matter when designing clinical trials:
- When does treatment need to begin?
- How much do PMP22 levels need to change?
- How can researchers detect a response before changes in nerve function can be measured?
These models will let researchers compare how CMT1A and CMT1E respond when treatment begins at different points. This gives the team a controlled way to compare treatment timing and measure the response in both types. Researchers can use what they learn to help plan future clinical trials, including when treatment begins and how much of a potential treatment to test.
The amount of correction matters, too. These models will help determine how much PMP22 levels need to change to improve symptoms without driving them too far. This gives researchers a clearer target for how much change a potential treatment needs to produce.
But knowing when to treat and how much change to aim for is only part of the challenge. Because CMT changes slowly over many years, researchers may have to wait a very long time to measure enough change to know whether a treatment is working. To help with this, the team will look for earlier biological signs, called biomarkers, that could provide an answer sooner.
Designing better clinical trials
These questions are becoming more important as therapies targeting PMP22 advance. Researchers need these answers to help turn potential treatments into clinical trials designed around what they know about CMT1A and CMT1E.
Clinical trials need clear measures to show whether a potential treatment is having an effect. For CMT1A and CMT1E, these models can give researchers information they need before a trial begins. They can test when treatment has the greatest effect, how much correction is needed, and what biological changes may signal a response. This gives researchers a stronger starting point when they move a potential treatment from the laboratory into studies with people.
What could this mean for people with CMT1A and CMT1E?
This project is designed to answer questions researchers need to solve so they can design better clinical trials for CMT1A and CMT1E.
The models will help determine when treatment should begin and how much PMP22 levels need to change. Biomarkers can give researchers an earlier way to see whether a potential treatment is affecting PMP22 biology before changes in nerve function are noticeable.
Together, these tools will help researchers know when to begin treatment, determine how much correction to aim for, and evaluate potential treatments sooner. Future clinical trials can then answer the question that matters most: Does the treatment work?
The information provided here is for informational purposes only and does not constitute medical advice. The CMTA does not endorse any specific products or treatments for CMT. Please consult your doctor before making any healthcare decisions.
