Vaccination Following Spinal Cord Injury: Innovative Approach Limits Paralysis


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Weizmann Institute scientists propose an innovative approach for preventing complete paralysis after partial spinal cord injury. The approach consists of boosting the body's natural immune mechanisms to improve the outcome of trauma.


The team of Prof. Michal Schwartz of the Weizmann Institute's Neurobiology Department has in the past already developed one immune-based therapy for the spinal cord, currently tested in humans by Proneuron Biotechnologies Ltd. That therapy is aimed at repairing the spinal cord after a complete injury. The new approach pursues a related but different therapeutic target: to limit degeneration after a partial spinal cord injury. The scientists report their latest results in the August 15 issue of the Journal of Clinical Investigation.


Following injury to the central nervous system (brain or spinal cord), a wave of damage spreads from the injury site over several days or weeks, killing nerve cells and fibers that survived the initial trauma. This secondary degeneration can be even more destructive than the initial damage. As a result, an injury that initially inflicted only partial damage on the nerve tissue in the spinal cord may eventually result in total paralysis.


In the United States alone, approximately 10,000 people sustain a spinal cord injury each year. More than half of these injuries are classified as incomplete, or partial, meaning that some nerve fibers survived the initial trauma. If the surviving tissue could be protected against secondary degeneration, this would significantly improve the final outcome.


In the past, Schwartz and colleagues showed that autoimmune T cells -- the white blood cells of the immune system that interact with the body's own tissues -- have a protective effect on damaged tissue in the spinal cord, reducing secondary degeneration. This protective response is the body's own way of minimizing the consequences of trauma. However, the naturally occurring T-cell response is restricted in its effectiveness.


In the new study, rats were vaccinated soon after severe partial injury to the spinal cord with peptides, or protein fragments, derived from the central nervous system. The peptides were selected so that they would boost the natural protective mechanisms of the immune system without triggering an autoimmune disease. Rats vaccinated with the peptides showed significant recovery of movement. Tissue analysis revealed that the treated animals had substantially more healthy nerve fibers in the spinal cord than the untreated rats, suggesting that the treatment protected the animals from secondary degeneration. Results indicate that the therapeutic window for T-cell-based treatment is at least on week after injury.


This approach may also prove effective in other disorders of the central nervous system, such as stroke or traumatic brain injury.


Professor Schwartz's team included Ehud Hauben, Eugenia Agranov, Amalia Gothilf, and Uri Nevo of the Weizmann Institute, and Avi Cohen and Igor Smirnov of Proneuron Biotechnologies Ltd. Her research is supported by Proneuron Biotechnologies Ltd., the Jerome and Binnette Lipper Medal, the Daniel Heumann Fund for Spinal Cord Research and in part by grants from the Glaucoma Research Foundation and the Alan T. Brown Foundation to Cure Paralysis. Michal Schwartz holds the Maurice and Ilse Katz Chair of Neuroimmunology.


The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel. Its 2,500 scientists, students and support staff are engaged in more than 1,000 research projects across the spectrum of contemporary science.