The Muscular Dystrophy Association (MDA) awarded more than $1 million to a new clinical trial (NCT03550300) to evaluate the potential of magnetic resonance imaging (MRI) in assessing muscle changes over time in patients with Charcot-Marie-Tooth disease.
The development of safe and effective therapies for CMT has been hampered by the lack of biomarkers that reflect disease response to investigative therapies tested in clinical trials. Because the disease progresses slowly, the potential effectiveness of therapies is difficult to assess.
Reilly and her colleagues aim to develop a new, more sensitive method that will allow researchers in clinical trials to detect the potential effects of therapy candidates within a short period of one to two years.
“The identification and validation of a biomarker that could detect disease changes in CMT over a 1-year period of time would be a critical advance that could shorten the length of clinical trials, reduce the number of participants needed to participate, attract more biotech and pharmaceutical companies to the CMT drug development space and, ultimately, lead to effective therapies,” Amanda Haidet-Phillips, PhD, scientific program officer at the MDA, said in a press release.
The team will evaluate the potential for magnetic resonance imaging (MRI) to detect the changes in muscle that affect CMT patients, including muscle weakness and wasting and accumulation of fat. The protocol developed by the UCL team will measure fat accumulation in thigh and calf muscles.
In a pilot study, the researchers showed that fat infiltration in the calf muscles of CMT patients significantly increased over one year and correlated with other markers of disease severity, including muscle strength.
Importantly, these changes were detected by MRI. The technique was able to detect disease worsening in CMT over a 12-month period in some patients, where other measurements failed, supporting its potential in clinical trials with CMT patients.
The new grant will allow researchers to follow up on these initial findings and refine the new protocol, testing its effectiveness in the foot muscles. In mild forms of CMT, fat accumulation is more often concentrated in the feet then the calve muscles.
“We are grateful to MDA for its support of this extremely important work,” Reilly said.
“The results from our pilot study of an MRI neuromuscular protocol in CMT1A are promising and we anticipate we will be able to confirm responsiveness with a refined protocol in children and in the other three common types of CMT,” she said.
The trial is aimed at children with CMT1 subtype A (CMT1A) — the most common subtype of CMT1, accounting for about 60 percent of CMT1 cases — but also other subtypes of the disease, namely CMT1 subtype B (CMT1B), Charcot-Marie-Tooth disease type 2A (CMT2A) and Charcot-Marie-Tooth disease type X (CMTX) patients.
“If successful, we will have developed a sensitive, validated, responsive outcome measure in CMT across international sites and across multiple forms of the disease in children and adults,” Reilly said. “This will have a major impact on our ability to conduct the clinical trials needed to efficiently and successfully test potential new therapies for CMT.”
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