Virus-mediated gene therapy has been used to treat a mouse model of Charcot–Marie–Tooth disease (CMT) type 4C in a recently published proof-of-principle study. Natasa Schiza and colleagues developed a lentiviral vector that was administered by intrathecal injection to mice in which the Sh3tc2 gene — mutation or truncation of which causes CMT type 4C — was knocked out. At 8 weeks after the injection, motor performance was better in mice that had been treated with the gene therapy than in those that had been treated with a mock lentivirus. Nerve conduction velocity, myelin morphology and nodal molecular architecture were also all improved, and blood levels of neurofilament light — a marker of axonal degeneration — were reduced. The study indicates that viral gene replacement therapy that targets Schwann cells could be used to treat CMT type 4C and possibly other similar demyelinating neuropathies.