Spinal cord injury (SCI) often results in permanent paralysis because there is little spontaneous repair. Neuronal injury in the
central nervous system (CNS) causes breakage of axonal connections, release of myelin, inflammation and cell death at the lesion site.
Many factors contribute to the failure of spontaneous repair after SCI, including the presence of growth inhibitory proteins in myelin, the
inflammatory environment of the injured CNS, and the resulting signaling cascades that result in over-activation of Rho, a signaling
switch in neurons and axons. In this review, we provide a general overview of growth inhibition in the CNS, and show evidence that most
growth inhibitory proteins signal through a common intracellular pathway. Rho is a convergent signal for growth inhibition, and also for
signaling some of the secondary consequences of inflammation after SCI. We review the preclinical evidence that targeting Rho is an effective
way to stimulate axon regeneration and functional recovery in preclinical animal models. In the last part of the review, we describe
the creation of Cethrin, a new investigational drug, and summarize the results of the Phase I/IIa clinical study to examine the
safety, tolerability and efficacy of Cethrin in patients with acute SCI. We conclude with some insight for future clinical studies.