The isolation and characterization of normal and abnormal proteins in the genetic disorders affecting the nervous system has permitted the isolation of cDNA and genomic DNA that can be used to investigate the correction of inherited protein deficiencies using recombinant DNA techniques. specifically somatic cell gene transfer. Particularly suited for initial attempts at gene therapy are those disorders (such as Gaucher disease, the most common sphingolipidosis) in which the manifestations of the disorder are due to abnormalities of hematopoietic cells. in this case, the macrophage. In this instance the transfer of normal genes to bone marrow progenitor cells is a rationale therapeutic approach. Using the lysosomal disorder Gaucher disease as a model, we have been successful in utilizing retroviral vectors to transfer and express human glucocerebrosidase in host mouse and Gaucher cell lines. The complete correction of glucocerebrosidase activity in Gaucher fibroblasts in culture has provided the impetus for evaluation of retroviral mediated somatic cell gene transfer of the glucocerebrosidase gene into mice by bone marrow transplantation. The initial goal of this research is the application of these recombinant DNA therapeutic strategies to the non-neuronopathic phenotypes. Animal models are being developed using recombinant technologies. When our understanding of the pathogenetic mechanisms of inherited neurological and psychiatric diseases improves and when retroviral-mediated expression of genes in specific tissues and cells become more predictable, we can begin to investigate the potential usefulness of gene therapy for treatment of selected disorders affecting the nervous system.
