Confocal image of a fibrotic scar, a major obstacle to axon regeneration, in a lesioned rat spinal cord. Image provided courtesy of F. Hellal and F. Bradke, Max Planck Institute of Neurobiology.
Two of the main processes that hinder spinal cord repair after injury are scar-tissue formation and lack of axon growth, and microtubule formation is a key component of both. Hellal et al. therefore investigated whether Taxol, a microtubule-stabilising drug that is widely used in cancer therapy to limit cell division, could reduce these effects following spinal cord injury (SCI). In rats, application of a low dose of Taxol at the site of SCI interfered with mechanisms important for scar formation, such as TGFβ signalling, transduction of which requires the microtubule network. In addition to decreasing scar formation, Taxol treatment reduced the amount of growth-inhibitory chondroitin sulfate proteoglycans at the lesion site, which together created an environment conducive to axon growth. Moreover, Taxol treatment induced axon regeneration, resulting in functional improvement. By targeting the cytoskeleton, at which growth inhibitory signals converge, rather than interfering with single inhibitory factors, Taxol could provide multi-targeted therapy for SCI, and has the advantage of being an approved drug. Future research will aim to discover whether regeneration is seen when the time between injury and treatment is increased.
