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Objective: To identify, review, prioritize and conduct experiments that replicate important published studies in SCI, and to compare the efficacy of different treatment paradigms in a standardized environment with a minimum variability in surgery, animal care, outcome evaluation, and cellular and molecular analysis.

Although numerous new findings herald the coming of many potential treatments for SCI, a barrier to the development of such avenues to treatments for patients is the lack of confirmation of the results. Novel and promising results from one laboratory have not been confirmed by replication in other laboratories or in other model systems. This inability to confirm and characterize potentially important outcomes with confidence has prevented new approaches from moving forward to clinical studies. To fulfill this need, this RIRC contract replicates and assesses promising published studies on SCI research and compares the efficacy of different individual treatments using conventional rodent models of SCI in an environment that provides standard and professional care for the test animals and standardized methods of evaluating return of function following injury.

There is general agreement about the critical need to replicate promising studies. At present, however, replication occurs randomly if at all, and generally requires that an individual investigator or group of investigators already is involved in ongoing studies that use nearly identical or at least very similar techniques and approaches. Because of the complexity of SCI research, and the fact that there is no established way to obtain funding for such studies, a full-scale replication is rarely if ever carried out. In recognition of the need for replication before moving to more translational types of endeavors, as a FOR-SCI, the Reeve-Irvine Research Center is carrying out full-scale replications of key published studies that are identified as crucial by a high level steering committee.

Replication 1: Lu, et.al (2002)

The first project selected for replication was Lu, J., Feron, F., Mackay-Sim, A., Waite, P.M.E., Olfactory ensheathing cells promote locomotor recovery after delayed transplantation into transected spinal cord, Brain, 125: 14-21, 2002. In this experiment, Lu et al reported that transplantation of olfactory lamina propria (OLP) containing olfactory ensheathing cells one month after a complete transection of the spinal cord at the thoracic level resulted in restoration of locomotor function and enhanced axon regeneration. We have completed the replication of this study and have submitted the manuscript for publication.

Replication 2: Li et al (2003)

The second project selected for replication was Li and Strittmatter, Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury, Journal of Neuroscience, 23: 4219-4227, 2003. In this experiment, Li and Strittmatter reported that delayed subcutaneous treatment with the NgR antagonist peptide NEP1-40 (Nogo extracellular protein, residue 1-40) results in enhanced locomotor recovery after thoracic spinal cord injury. They observed extensive growth of corticospinal axons, sprouting of serotonergic fibers, up regulation of axonal growth protein SPRRIA (small proline – rich repeat protein 1A) and synapse re-formation. Replication is underway.