Summary

• Spinal cord injury (SCI) can lead to paraplegia or quadriplegia and is a devastating condition for which there is as yet no cure. Cellular and molecular, as well as rehabilitative training, therapies are being developed in animal models, and some are now in, or moving towards, clinical trials.
• Cellular therapeutic interventions after SCI include transplantation of peripheral nerve cells, Schwann cells, cells from the olfactory nervous system, stem/progenitor cells and activated macrophages.
• Molecular therapeutic interventions after SCI include neuroprotective therapies, axonal conduction enhancement, growth factor delivery, cyclic AMP delivery, small GTPase delivery, and therapies that modulate interactions with myelin inhibitors and extracellular matrix modifiers.
• Some of these interventions are still at the animal experimental stage. However, there are interventions that are progressing to potential application in humans through the use of human cells in animal models (for example, transplantation of Schwann cells, and stem/progenitor cells). Some therapies are already in clinical trials to treat other diseases (for example, administration of nerve growth factor in the treatment of Alzheimer's disease).
• Other potential therapies are already in, or progressing towards, clinical trials, including transplantation of cells from the olfactory nervous system, bone marrow stromal cells and activated macrophages. The potential of 4-aminopyridine, Cethrin and Nogo-A antibodies is also being tested.
• Improved locomotor function can be achieved with rehabilitation, because the spinal circuitry below the lesion site maintains active and functional neuronal properties, such that it can generate oscillating, coordinated motor patterns and is capable of considerable plasticity. Many SCI clinical trials are currently addressing aspects of rehabilitation, including upper-extremity exercise, body-weight-supported treadmill training and/or functional electric stimulation.
• However, much work remains to be done to determine whether any of these therapies can safely improve outcome after human SCI. To identify therapies that are unambiguously safe and effective, the scientific and clinical SCI communities increasingly recommend that preclinical studies should be reproduced by independent laboratories. Finally, individual therapies are unlikely to emerge as a sole cure. Rather, we predict that combinations of strategies will lead to collective improvement in outcome after SCI.