Need for a paradigm shift in therapeutic approaches to CNS injury.

Irreversible damage to the nervous system can result from many causes including trauma, disruption of blood supply, pathogen infection or neurodegenerative disease. Common features following CNS injury include a disruption of axons, neuron death and injury, local B-cell and microglial activation, and the synthesis of pathogenic autoantibodies. CNS injury results in a pervasive inhibitory microenvironment that hinders regeneration. Current approaches to eliminate the inhibitory environment have met with limited success. These results argue for a paradigm shift in therapeutic approaches to CNS injury. Targeting CNS cells (neurons, oligodendrocytes and astrocytes) themselves may drive CNS repair. For example, our group and others have demonstrated that autoreactive antibodies can participate in aspects of CNS regeneration, including remyelination. We have developed recombinant autoreactive natural human IgM antibodies with the therapeutic potential for CNS repair in several neurologic diseases.