Possible T Cell Immune Response to AAV Treatment in non-Human Primates with Spinal Cord Injury
Open Access Senior Thesis
Bachelor of Arts
W.M. Keck Science Department
© 2012 Laura Wyatt and Ephron Rosenzweig
Neurons in the spinal cord do not spontaneously regenerate, which often leads to debilitating injuries. One method proposed to promote axonal regeneration is the injection of viruses carrying genes for growth factors into the injured spinal cord. One such virus, the adeno-associated virus (AAV), has shown promise in gene therapy medical research. However, injecting AAV into rhesus macaques with C7 spinal cord hemisection lesions actually leads to motor neuron loss in the gray matter of the spinal cord, rather than contributing to the preservation or regeneration of axons. This unexpected result highlights the necessity of further testing with therapeutic approaches for axon regeneration in nonhuman primate models before moving into clinical trials. It is possible that an immune-related T cell response to the AAV-transfected cells causes this motor neuron loss. T cells are white blood cells that play a role in attacking cells infected with viruses. It is unknown whether such a response of the immune system to respond with an up-regulation of T cells may be taking place over a relatively short period (weeks) or over many months. This question was tested here: T cells were stained in spinal cord sections caudal (below) the lesion in the spinal cord and near AAV injection sites to determine whether there was a greater quantity of T cells in these areas compared to the subject’s baseline levels. Subjects that had AAV therapeutic injections and that were examined 6 months after the injection were found to have greater quantities of T cells than those who did not have injections containing AAV. It was also found that the AAV-injected subjects examined only 6 weeks post injection did not have greater quantities of T cells than control subjects. These results suggest that there may be a delayed immune response to the AAV injections in nonhuman primates with spinal cord injury, which occurs over a period of months. Pinpointing the mechanism that causes this cell death would allow researchers to create a safer therapeutic that could promote axonal growth in people with spinal cord injuries.
Wyatt, Laura and Rosenzweig, Ephron, "Possible T Cell Immune Response to AAV Treatment in non-Human Primates with Spinal Cord Injury" (2013). Scripps Senior Theses. 163.