CMT1B and CMT1E can take away strength, feeling, and balance from damage to the nerve cells over time. A new CMTA research project asks whether an already approved drug, paired with a new drug candidate, can stop or slow down this damage.
CMTA is investing $225,720 in this work, led by Maurizio D’Antonio, PhD, at Ospedale San Raffaele in Milan, Italy.
Two CMT treatments, one target
In CMT1B and CMT1E, faulty genes cause peripheral nerve proteins to misfold. When misfolded proteins pile up inside cells, they overwhelm the proteasome (pro-tee-uh-zohm), the cell’s clean-up system, and the nerve loses function over time.
D’Antonio’s team will test two treatments that target this clean-up system directly. The first is a PDE5 inhibitor, a drug the FDA already approved for another disease. Because it already has years of safety data, it can potentially reach patients faster and at a lower cost than a brand-new drug. This approach is called drug repurposing. The second treatment is a new experimental medicine from a CMTA Strategy to Accelerate Research (CMTA-STAR) Alliance Partner.
This project builds on CMTA-funded research in CMT1A led by Jordan VerPlank, PhD. That work targets the same clean-up pathway and has restored proteasome activity and improved nerve function in early laboratory studies. The D’Antonio lab will test whether the same strategy works in CMT1B and CMT1E, and possibly in other forms of CMT.
“We are grateful to the Charcot-Marie-Tooth Association for supporting this work, which addresses a critical gap in our understanding of how CMT1B and CMT1E damage the peripheral nerve,” says D’Antonio. “This project is designed to define how disrupted protein handling contributes to peripheral nerve damage and to determine whether restoring this system could be developed into a treatment strategy for these subtypes and potentially others.”
This study extends CMTA’s work in CMT1A to CMT1B and CMT1E subtypes to determine if this approach has broader application across multiple CMT subtypes. “By connecting ongoing research at the VerPlank lab to this new project at the D’Antonio lab,” says CMTA Chief Research Officer Katherine Forsey, PhD, “We are uniting researchers around a shared biological approach that aims to move medicines to patients faster. If successful, this approach could help create new treatments for people living with CMT.”
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