UC Primate Consortium: Axonal Plasticity and Regeneration
Mark Tuszynski, M.D., Ph.D., UCSD
Director & Professor, Center for Neural Repair, Department of Neurosciences
Ephron Rosenzweig, Ph.D.
Asst. Project Scientist, Center for Neural Repair, Department of Neurosciences

This is a collaborative project among five UC campuses (UC San Diego, UCLA, UC Irvine, UC Davis and UCSF) that aims to achieve two objectives. First, we will develop a model of chronic primate spinal cord injury to speed the development of promising therapies for humans. Second, this project will test whether growth factor gene delivery will enhance anatomical and functional recovery after chronic injury.

Progress in the field of SCI research has been substantial in the last decade, and several experimental manipulations have been reported to enhance functional recovery after SCI in animal models. Included in such reports are stem cells, olfactory ensheathing cells, neutralizers to inhibitors of regeneration (including both myelin- and ECM-associated inhibitors), growth factor gene delivery to stimulate axon growth, cAMP stimulation, and use-dependent plasticity. However, the relevance of findings from rodent models to the larger human spinal cord remains unclear. There are distinct differences between rodent and primate spinal cord systems, including: 1) Size. Regeneration of an injured axon in the rat over several millimeters might be sufficient to generate functional recovery, whereas distances of many centimeters might be required in the primate spinal cord. 2) Anatomy. There are differences in the number, location and termination patterns of important axonal systems such as the corticospinal tract in primates compared to rodents. 3) Function. Some important axon systems have different functional roles in primates and rodents. For example, the corticospinal tract is critical for most movement in humans, but not in rats. On the other hand, the rubrospinal tract is important for forelimb movement in rats but is vestigial in humans. 4) Inflammatory responses and secondary injury. Although not well characterized, the intensity and nature of inflammation and secondary damage may differ in rodent and primates species due to differences in immune complexity and molecular (e.g., cytokine) recruitment to injury sites.

The goal of this research program is to examine injury, plasticity and regeneration in the chronically injured adult primate spinal cord so that we can initiate a rational movement of potential therapies, and synergistic therapies, to humans. The work of this consortium will both focus on enhancing our mechanistic understanding of injury to the primate spinal cord, and on developing practical and validated therapies that could undergo human testing in the future.

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