A major focus of the Neurogenetics Laboratory is the study of the biochemical and molecular causes of inherited diseases and more effective means for their treatment. In the past few years, our laboratory has characterized a variety of novel mutations responsible for the G_M2-gangliosidoses and globoid cell leukodystrophy. In vitro mutagenesis and transfection into COS cells allow us to clarify genotype: phenotype relationships in these and related lysosomal storage diseases and in animal models of these diseases. We are also involved in collaborations to investigate the gene loci for mucolipidosis IV and familial spastic paraparesis.

Gene therapy is being developed in our laboratory as a tool in the treatment of malignant brain tumor, Parkinson's disease and the lysosomal storage diseases. Glioma cells transduced with recombinant retroviruses expressing cytosine deaminase become sensitive to the prodrug 5-fluorocytosine and this effect is enhanced by interferons. Using this same suicide gene approach in combination with a vector, expressing both cytosine deaminase and thymidine kinase has enabled us to significantly prolong the survival of rats with rapidly growing intracerebral glioma. We also participate in a consortium devoted to the use of another form of gene therapy, bone marrow transplantation, to successfully treat globoid cell leukodystrophy.

Our work in lysosomal storage diseases has also led us to discover molecular mimicry between antiglycolipid antibodies found in various autoimmune diseases such as multiple sclerosis and certain proteins including p24 and gp120 of the HIV virus and various brain cell membrane components. The gene for one such protein, GCP, has been cloned and its structural relationship to the galactolipids is being investigated.