Need for a paradigm shift in therapeutic approaches to CNS injury

Abstract

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

Keywords::

• Alzheimer’s disease
• antibodies
• brain injury
• catalytic antibodies
• CNS injury
• ischemia
• multiple sclerosis
• natural autoantibodies
• spinal cord injury
• stroke
• therapeutic strategies

Financial & competing interests disclosure

This work was supported by grants from the NIH (R01s – GM092993, NS024180, NS032129, NS048357, R21 – NS073684), the National Multiple Sclerosis Society (CA1060A11), the Applebaum Foundation, the Hilton Foundation, the Peterson Foundation, Minnesota Partnership for Biotechnology and Medical Genomics and the European Regional Development Fund – Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123). The authors also thank the McNeilus Family and a High-Impact Pilot and Feasibility Award (HIPFA) from the Mayo Clinic Center for Translational Science Activities (CTSA) for financial support in this project. B Wootla is the recipient of a fellowship from the Mayo-Applebaum funds. The technology for remyelination-promoting antibody rHIgM22 has been licensed to Acorda Therapeutics, Inc. No royalties have accrued to M Rodriguez or Mayo Clinic to date, but both have rights to receive future royalties. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.