Natural History Study of CMT4J Aims to Support Future Development of Gene Therapy Trial

The first patient has been enrolled in what’s regarded as the first natural history study of Charcot-Marie-Tooth disease type 4 (CMT4J), with the ultimate goal of one day developing a gene therapy for the disease, announced the study’s collaborators, Neurogene and UT Southwestern Medical Center.

The study’s short-term goal is to gain key data to support a future gene therapy trial. Natural history is the usual development course of a disease or condition, especially in the absence of treatment.

“Patients with CMT4J and their families have been waiting for a therapy, and we view this study as a critical component of the clinical development plan to address that unmet need,” said Effie Albanis, MD, Neurogene’s chief medical officer, in a news release.

“We are taking a streamlined approach to clinical development to facilitate the fastest approval timeline for a future gene therapy medicine, consistent with our belief that patients should not be waiting longer than necessary for life-altering medicines,” she added.

CMT4 is a rare type of CMT that causes damage to the myelin sheath, an insulating fat-rich layer surrounding the axons of peripheral nerve cells that connect the brain and spinal cord to motor and sensory muscles. The disease causes muscle weakness and sometimes changes in sensations. With varying degrees of disease severity, patients may also develop symptoms such as cataracts or deafness.

Disease subtypes include CMT4J, which is caused by mutations in the FIG4 gene that encodes for a protein called Fig4. Researchers are working to determine how mutations in this gene lead to the specific signs and symptoms of CMT4J. Disease symptoms and age of onset vary.

Researchers have yet to develop a treatment that addresses the condition’s underlying cause. Current therapies — none of which is a medication — aim to help patients to manage the disease and maintain their quality of life.

The five-year prospective observational study (NCT03810508) is looking to enroll about 20 CMT4J patients at UT Southwestern Medical Center. Participants will undergo multiple tests including a series of disease measurements, magnetic resonance imaging, and nerve conduction and pulmonary function assessments.

The study’s purpose is to investigate the clinical characteristics and progression of symptoms in order to better understand the disease’s course and determine appropriate outcome measures for future trials.

“This is the world’s first prospectively designed natural history study specifically for CMT4J,” said Diane Castro, MD, assistant professor at UT Southwestern and lead study investigator. “With the help of the patients participating, this work will generate invaluable data to help us define optimal endpoints for a future planned gene therapy trial.”

Charcot-Marie-Tooth disease affects about one in 2,500 people in the United States and 2.6 million globally.