Molecular therapy of neurodegenerative diseases.
Lysosomal storage diseases comprise a group of over forty related disorders that result from dysfunction of lysosomal enzymes or associated proteins. With a frequency of 1 in 7700 live births, these inherited diseases often occur in early childhood and most are currently untreatable. Dr. Martin studies therapeutic strategies for the neuropathic lysosomal storage diseases known as GM1 and GM2 gangliosidosis in well-characterized feline models. Although many types of molecular therapy are being considered, the laboratory focuses primarily on adult stem cell and/or gene therapy with lentiviral or adeno-associated viral vectors. Because normal or genetically engineered donor cells can transfer lysosomal enzymes to diseased cells through a process known as "cross-correction," stem cells are being evaluated as enzyme delivery vehicles. In a more direct approach, replication-defective viruses engineered to express a therapeutic lysosomal enzyme are used to restore enzymatic activity. Dr. Martin and collaborators expect that positive results in the feline model will lead to human clinical trials for these devastating diseases.