Other Diseases The power and versatility of gene transfer approaches are such that there are few serious disease entities for which gene transfer therapies are not under development. Besides those already discussed, other areas of interest include gene therapies for HIV and for neurodegenerative disorders. The latter include studies in patients with Parkinson's disease, where AAV vectors expressing enzymes required for enhanced production of dopamine, or of the inhibitory neurotransmitter γ-aminobutyric acid, have been introduced into affected areas of the brain (striatum, subthalamic nucleus) by stereotactic neurosurgery. In Alzheimer's disease, an ex vivo approach in which autologous fibroblasts are transduced. | Chapter 065. Gene Therapy in Clinical Medicine Part 5 Other Diseases The power and versatility of gene transfer approaches are such that there are few serious disease entities for which gene transfer therapies are not under development. Besides those already discussed other areas of interest include gene therapies for HIV and for neurodegenerative disorders. The latter include studies in patients with Parkinson s disease where AAV vectors expressing enzymes required for enhanced production of dopamine or of the inhibitory neurotransmitter y-aminobutyric acid have been introduced into affected areas of the brain striatum subthalamic nucleus by stereotactic neurosurgery. In Alzheimer s disease an ex vivo approach in which autologous fibroblasts are transduced with a retroviral vector expressing nerve growth factor then reimplanted into the basal forebrain has slowed the rate of cognitive decline in a small Phase I study. Summary The development of new classes of therapeutics typically takes two to three decades monoclonal antibodies and recombinant proteins are recent examples. Gene therapeutics which entered clinical testing in the early 1990s are well along in the course of development and are likely to become increasingly important as a therapeutic modality in the twenty-first century. A central question to be addressed is the long-term safety of gene transfer and regulatory agencies have mandated a 15-year follow-up for subjects enrolled in gene therapy trials Table 65-3 . Realization of the therapeutic benefits of the Human Genome Project and of new discoveries such as RNAi will depend on continued progress in gene transfer technology. Table 65-3 Taking History from Subjects Enrolled in Gene Transfer Studies Elements of History for Subjects Enrolled in Gene Transfer Trials 1. What vector was administered Is it predominantly integrating retroviral lentiviral herpesvirus latency and reactivation or non-integrating plasmid adenoviral AAV 2. What was the route of .
