Grant Will Help Scientist Develop MRI Biomarkers of CMT1A

Scientist Jun Li has won a $246,172 grant to develop new MRI biomarkers to assess disease progression and response to treatment in people with Charcot-Marie-Tooth disease type 1A (CMT1A).

The grant, from the National Center for Advancing Translational Sciences of the National Institutes of Health, will fund a project titled “MRI Biomarkers of Disease Progression in Inherited Neuropathies.”

The research is led by Li, MD, PhD, professor and chair of the department of neurology at Wayne State University School of Medicine, in Detroit, together with Richard Dortch, PhD, of the Barrow Neurological Institute at Dignity Health St. Joseph’s Hospital and Medical Center, in Phoenix.

The most common form of the disease, CMT1A is characterized by the loss of myelin in the peripheral nervous system — the nerves connecting the brain and the spinal cord to other regions in the body. Myelin is a fatty substance that surrounds the nerve cells like a sheath, protecting them and aiding in the efficient transmission of electrical signals.

CMT is part of a large group of disorders called neuropathies, which are diseases characterized by nerve damage that affects nerve function.

While the development of therapies for CMT is on the rise, the lack of reliable biomarkers of disease progression in people with CMT1A poses an obstacle to testing treatment efficacy.

“Although there are promising treatments for CMT, evaluations of potential treatments are hindered by a lack of responsive biomarkers,” Li said in a press release.

MRI imaging can be used to assess abnormal changes in nerves. Li and Dortch and their team are using an MRI technique called magnetization transfer ratio or MTR — which allows them to directly image the pathology or disease development of interest within the nerves themselves. This technique has been shown to correlate with disability across CMT subtypes when analyzing the sciatic nerve, which extends from the spinal cord through the legs.

“Our research aims to focus on nerve MRI methods that we have developed to offer important information and improve our ability to monitor disease progression in patients through MRI-based biomarkers of CMT,” Li said.

Previous data has shown that MTR is sensitive to the loss of myelin and nerve fibers (axons). Also, preliminary findings suggest that MTR can reflect disease progression, and that nerve diameter — as assessed by MRI — can work as specific biomarker of CMT1A.

Questions that the project will address include the relationships between candidate biomarkers and patients’ function, nerve conduction, disease-related changes (as assessed by skin biopsy), and quality of life. The scientists also will look at whether imaging biomarkers of nerve or muscle generate reliable results across different sites.

The end goal, the researchers say, is to develop new imaging biomarkers to be used in clinical trials in CMT1A to further potential treatments.