The revised application now has five major aims: to generate syngeneic fibroblasts that contain a retroviral construct that encodes a PLP-miniprotein; to determine the potential amelioration of clinical signs and histologically-measured CNS inflammation provided by these fibroblasts; to determine the immune status of the treated animals versus controls to determine if there is evidence for intramolecular and intermolecular determinant spreading; to determine a direct correlation with the therapeutic effects of the fibroblasts and their ability to down-regulate IL-2 (and other cytokine) synthesis in the brains of treated and control mice with EAE; and finally to construct a hybrid vector containing epitopes from both PLP and MBP.
Louie, K A; Weiner, L P; Du, J et al. (2005) Cell-based gene therapy experiments in murine experimental autoimmune encephalomyelitis. Gene Ther 12:1145-53 |
Weiner, Leslie P; Louie, Katherine A; Atalla, Lilly R et al. (2004) Gene therapy in a murine model for clinical application to multiple sclerosis. Ann Neurol 55:390-9 |