CMTA is proud to share that research led by CMTA Strategy to Accelerate Research (CMTA-STAR) Scientific Advisory Board member Maurizio D’Antonio, PhD, has been published in the leading scientific neurology journal, Brain. With CMTA funding support, this study highlights the critical role of the unfolded protein response (UPR) transcription factor XBP1 in CMT1B and suggests it may be a promising therapeutic target not only for CMT1B but also for other demyelinating forms of CMT, including CMT1A and CMT1E.
In CMT1B, mutations in the MPZ gene can cause Schwann cells, which produce and regulate peripheral nerve myelin, to experience stress due to the buildup of misfolded proteins. A misfolded protein is one that has not formed into its correct shape, preventing it from working properly and disrupting normal cell function. Dr. D’Antonio and colleagues have demonstrated that activating XBP1 helps Schwann cells clear out these misfolded proteins, maintaining cell health and supporting proper myelination. This finding offers a potential pathway for future treatment approaches.
“Our research shows that XBP1 plays a key role in helping Schwann cells manage cellular stress and maintain peripheral nerve myelin health in CMT1B. When this pathway is disrupted, disease severity worsens, but by increasing XBP1 activity, we may be able to protect Schwann cells and improve nerve function. This could be an encouraging therapeutic approach not only for CMT1B but also for other demyelinating neuropathies like CMT1A and CMT1E. CMTA’s support has been fundamental in allowing us to explore these mechanisms and advance potential treatment strategies,” said Dr. D’Antonio.
“This research provides critical insight into how Schwann cells respond to cellular stress in CMT and uncovers an encouraging pathway to protect myelin and preserve nerve function,” said Katherine Forsey, PhD, CMTA Chief Research Officer. “Every breakthrough like this brings us closer to treatments, and it is only possible because of the generosity and dedication of the CMTA community in funding CMTA-STAR.”
CMTA remains dedicated to funding research that uncovers new treatment strategies with the potential to benefit multiple types of CMT. By supporting studies like this, CMTA-STAR continues to accelerate discoveries that not only advance our understanding of disease mechanisms but also lay the groundwork for future therapies that could improve the lives of everyone living with CMT.
Stay informed about the latest CMT research and CMTA-STAR advancements by signing up for CMTA eNews. Click the eNews button below to get updates delivered straight to your inbox.
CMTA congratulates Dr. D’Antonio and his team on this important achievement. To read the full publication, visit D’Antonio et al. Identify XBP1 as a Potential Therapeutic Target for CMT
Published on: April 10, 2025