With CMTA support of $440,637, researchers led by Jordan VerPlank, PhD, at the Uniformed Services University of the Health Sciences (USUHS) are building on prior CMTA-funded work in the lab of the late Laura Feltri, MD, to explore ways to reactivate proteasomes (proh-tee-uh-sohm), the cellular machinery that clears toxic proteins.
In CMT1A and CMT1B, reduced proteasome activity allows harmful proteins to build up in Schwann cells, disrupting myelin and damaging peripheral nerves. Schwann cells are specialized cells that make and regulate peripheral nerve myelin.
Earlier CMTA-supported studies showed that raising levels of cyclic GMP (cGMP), a molecule that regulates proteasome activity, improved myelin thickness, nerve function, and motor coordination in models of CMT1A & CMT1B when tested with the investigational compound CYR119. Building on these findings, Dr. VerPlank’s team is now evaluating an FDA-approved drug to raise cGMP levels as a potential therapy to restore proteasome activity and improve nerve health.
What are Proteasomes?
Dr. VerPlank breaks down his CMTA-funded research into plain language at the 2025 CMTA Patient and Research Summit: what proteasomes are, why they stop working in CMT1A & CMT1B, and how medicines already used in people can restore myelin thickness and nerve conduction in mouse models of both CMT1A & CMT1B.
March 2026 Update
The VerPlank lab has made progress on two fronts: further defining how cyclic guanosine monophosphate (cGMP) improves CMT1A & CMT1B in disease models and testing medicines that increase cGMP. Using gene-edited rat Schwann cells, the team showed that increasing cGMP reduces PMP22 levels by increasing its degradation. This effect occurred within one hour of treatment. These findings add to the understanding of how drugs that increase cGMP improve CMT1A & CMT1B in models.
Additionally, the VerPlank lab treated CMT1A mice with three medicines that increase cGMP through different mechanisms. Ongoing evaluation of these will help determine whether targeting cGMP could be a treatment strategy for CMT1A and CMT1B, and which mechanism of action may be most effective for future development.
