CMTA backs new CMT repurposing study with $225,720

The Charcot-Marie-Tooth Association is funding a new $225,720 study in Milan to test two repurposed treatments for CMT1B and CMT1E. The work could expand a protein-clearance strategy already being explored in CMT1A and speed potential therapies for a disease with no approved treatment.

Why it matters: - Charcot-Marie-Tooth disease has no approved treatment, so faster and cheaper drug development paths matter for patients living with progressive weakness, sensory loss and balance problems. - CMTA’s latest investment could broaden a repurposing strategy across multiple CMT subtypes, not just CMT1A. - If the approach works, the research could help move a treatment concept into the clinic sooner because repurposed drugs already have safety data.

What happened: - The Charcot-Marie-Tooth Association announced a $225,720 research investment in a study led by Maurizio D’Antonio, PhD, at Ospedale San Raffaele in Milan, Italy. - The project will test two treatments in CMT1B and CMT1E for their ability to restore peripheral nerve function by improving protein-clearance machinery in Schwann cells. - One treatment is an FDA-approved phosphodiesterase type 5 inhibitor that increases cyclic GMP levels. - The second treatment is a therapeutic candidate from a CMTA-STAR Alliance Partner.

The details: - In CMT1B and CMT1E, gene mutations cause peripheral nerve myelin proteins to misfold and accumulate inside Schwann cells. - That buildup stresses the proteasome, the cell’s main system for clearing damaged proteins, and contributes to peripheral nerve degeneration. - CMTA-funded work led by Jordan VerPlank, PhD, is already examining this pathway in CMT1A. - The VerPlank research has shown that targeting the pathway with a repurposed medicine restores proteasome activity and improves peripheral nerve function in preclinical CMT1A models. - The D’Antonio lab will test whether the same strategy works in CMT1B and CMT1E and possibly other forms of CMT. - The project supports a CMTA-STAR goal of targeting shared biological pathways across multiple CMT subtypes.

Between the lines: - The funding links two parts of CMTA’s research strategy: reuse of existing drugs and identification of shared disease biology across subtypes. - The approach is designed to reduce risk by starting with treatments that already have established safety profiles. - CMTA also appears to be using its STAR Alliance network to bring in additional candidate therapeutics from industry alongside academic research. - If the biology holds across subtypes, the same mechanism could have wider relevance than a single-gene or single-subtype program.

What’s next: - The D’Antonio lab will test whether boosting protein-clearance machinery can improve peripheral nerve function in CMT1B and CMT1E models. - Researchers will also assess whether the strategy could extend to other CMT subtypes. - CMTA said a successful result could open the door to new treatment options for people living with CMT.

The bottom line: - CMTA is betting that a shared protein-clearance target and repurposed drugs can speed therapies toward patients with multiple forms of CMT.