With CMTA support of $225,720, researchers led by Maurizio D’Antonio, PhD, at Ospedale San Raffaele in Milan, Italy, are evaluating whether a drug repurposing strategy can restore peripheral nerve function in CMT1B and CMT1E. The project will test an FDA-approved phosphodiesterase type 5 (PDE5) inhibitor that raises cyclic GMP (cGMP) levels, along with a therapeutic candidate provided by a CMTA Strategy To Accelerate Research (CMTA-STAR) Alliance Partner.
In CMT1B and CMT1E, mutations cause peripheral nerve myelin proteins to misfold and accumulate inside Schwann cells, disrupting the proteasome, the cell’s protein-clearance system. This project builds on ongoing CMTA-funded research led by Jordan VerPlank, PhD, which showed that restoring proteasome activity through cGMP signaling improved peripheral nerve function in preclinical CMT1A models. The D’Antonio will determine whether the same approach can be applied to CMT1B and CMT1E and potentially other forms of CMT that share this underlying biological mechanism.
