The Molecular Therapeutics Section was established in January 1994 to develop novel therapeutic approaches to viral and neurodegenerative diseases of the CNS. The approaches to be taken by this Section are outlined as follows: 1) Development and Transplantation of Neuroglial Cell Lines: An immortalized human fetal astrocyte cell line previously developed in this Laboratory has been successfully grafted into the basal ganglia of Sprague-Dawley rats and the subhuman primate, rhesus macaque. No tumor formation or obvious inflammatory response was seen. Experiments are being initiated in which MPTP-lesioned macaques would have this immortalized human fetal astrocyte cell line grafted to the basal ganglia in an attempt to reverse the parkinsonian symptoms by induction of neuronal sprouting. Efforts will also be directed towards understanding the immune response to these xenografts and the implications for human transplantation. 2) Development of a Novel Viral Vector for Gene Transfer into the CNS: Delivery of genes to selected cell populations within the CNS could potentially be used as a means for targeted delivery of therapeutic agents. Given that JC virus expression is restricted in the brain to cells of glial origin, we have constructed a novel chimeric JCV which expresses a cloned gene of interest in cells of glial origin but fails to replicate. This chimera has the same host range as wild type JCV and consequently could be used to deliver antiviral compounds to JCV infected glial cells in a patient with PML. 3) Development of Immunotherapy Targeted Against Viral Diseases of the CNS: Experiments are now in progress to determine whether we can initiate an immune response that will clear JCV from the CNS by expressing noninfectious viral antigens in the skeletal muscle of a patient with PML. A plasmid capable of expression of JCV structural antigens in skeletal muscle of a patient with PML. A plasmid capable of expression of JCV structural antigens in skeletal muscle has been constructed and is being tested in vitro. In vivo experiments are to follow.
