Progress in treating CMT depends on finding therapies that work and measuring how well they are working. This is harder than it sounds, and it is one of the reasons CMTA is investing in research that – at first – may seem unexpected.
Recently, CMTA funded a two-year study led by Gabriel Corfas, PhD, at the Kresge Hearing Research Institute at Michigan Medicine. The study will examine whether people with CMT experience forms of hearing loss that standard hearing tests may miss, and what that could reveal about how CMT affects the nervous system more broadly.
Why outcome measures are important
Before understanding why this study matters, it helps to understand what outcome measures are and why they are so important in clinical trials.
An outcome measure is a way of detecting and measuring change in a patient over time. In a clinical trial, researchers need reliable outcome measures to determine whether a treatment is having an effect. If the measures are not sensitive enough to detect subtle changes, a treatment that is actually working may appear not to be, and potentially promising therapies can stall as a result.
Current outcome measures for CMT clinical trials have limitations. Many rely on physical assessments such as balance or walking tests, which can be difficult to measure accurately, slow to show change, and may not reflect what is happening at the nerve level. Finding outcome measures that detect changes in nerve function earlier and more precisely is an active area of research that directly influences how quickly effective treatments can be identified and approved.
The connection between hearing, balance, and CMT
Balance problems are one of the most common and disruptive symptoms of CMT. Balance is controlled not only by the muscles and nerves of the legs and feet. A significant part of the body’s balance system originates in the inner ear, which sends signals to the brain about movement and spatial position.
The inner ear is also responsible for hearing. The nerve cells involved in both functions are peripheral nerve cells — the same type of cells affected by CMT. Recent research has suggested that people with CMT1A may experience a form of hearing difficulty called hidden hearing loss, which does not show up on standard hearing tests but affects the ability to understand speech in noisy environments and to locate the direction of sounds.
One of the great things about the ear is that we have very precise and sensitive methods and tools to non-invasively measure changes inside it. If CMT1A affects the nerve cells involved in hearing and balance in measurable ways, those measurements could serve as sensitive indicators of how the disease is progressing, and potentially of how well a treatment is working.
What the study will do
The research will take place in two phases.
The first phase is a survey open to people living with CMT1A. It will capture daily experiences with hearing, balance, and communication to build a broader picture of how these symptoms show up in real life.
The second phase will invite adults age 50 and under with CMT1A for in-person testing in Michigan. Participants will undergo hearing assessments that include tests to determine how well they can understand speech in noisy settings and locate sound direction. They will also complete balance assessments. Results will be compared to those of individuals without CMT1A to determine whether hidden hearing loss is associated with the disease.
Impact beyond CMT1A
Although this study focuses on CMT1A, the underlying questions it is asks are relevant to the broader CMT community. Balance problems affect people across many types of CMT, and the challenge of finding sensitive, reliable outcome measures for clinical trials is not specific to any one genetic cause of the disease. If this research demonstrates that inner ear function can serve as a meaningful indicator of nerve health, it could open the door to new approaches to measuring treatment effects across CMT types. It could also support a new standard of care, ensuring people with CMT are routinely tested for hearing loss.
Looking ahead
The goal of this study is to build a more precise way of measuring whether treatments are working. The more outcome measures researchers have available, the better equipped they are to detect whether a therapy is having an effect in a clinical trial, and to make a strong case for it being approved by the regulators.
