This proposal is focused on gene therapy approaches for lysosomal storage diseases affecting the D central nervous system. Using late infantile neuronal ceroid lipofuscinosis (LINCL / Batten Disease) as a D model disease, I propose to test hypotheses regarding delivery of a gene to the CNS of a murine disease D model. Recent data from our lab shows that adeno-associated virus type 4 (AAV4) is effective in directing D widespread distribution of a lysosomal enzyme in the murine brain, which is an exciting finding given that D LINCL patients exhibit widespread CNS pathology. The ability of AAV4 to direct gene transfer in a mouse D model of LINCL will be tested here. In addition, I propose to develop a tetracycline-regulated viral vector as I clinical applications of gene transfer will likely require regulated expression to minimize immune responses C or other adverse effects. A regulated vector will also allow me to address the duration of benefits after D cessation of enzyme expression. ? ? ?
| Chang, Michael; Cooper, Jonathan D; Sleat, David E et al. (2008) Intraventricular enzyme replacement improves disease phenotypes in a mouse model of late infantile neuronal ceroid lipofuscinosis. Mol Ther 16:649-56 |
