Frontotemporal dementia (FTD) is a devastating early-onset dementia (peak incidence in the 50's) characterized by loss of insight, impaired judgment, lack of inhibition, and inappropriate social behavior. It is the second most common form of dementia in persons under 65. FTD progresses rapidly and median survival time after diagnosis is approximately 6 years. There are no means of prevention, cure, or effective treatment.Approximately 5-10% of FTD is caused by mutations in the GRN gene coding for the protein progranulin. Progranulin supports nerve cell survival and function. One copy of a GRN mutation associated with FTD results in diminished brain progranulin production leading to extensive neuronal dysfunction and inflammation.Provectra Therapeutics Inc (Provectra) is developing adeno-associated virus (AAV) vectors to increase progranulin levels in brains of patients with GRN- FTD. We will use an engineered virus particle containing the normal GRN gene that efficiently crosses the blood-brain barrier with high selectivity for brain tissue. Data from both rodents and non-human primates indicate that a single injection of an AAV2.5 containing a marker gene into cerebrospinal fluid causes effective protein production throughout the brain and spinal cord. The vector system has been described as a molecular FedEx where the nucleocapsid provides the "address" with the gene being the "message".AAV vector systems have been used in a number of clinical studies. There have been no treatment-related adverse events attributable to treatment agent. There has been abundant FDA guidance for this approach to CNS gene therapy.Provectra will use this clinically validated platform technology to treat GRN- FTD. We plan to optimize the AAV2.5-GRN construct and determine response to a single dose in cerebrospinal fluid with respect to: safety, biodistribution, and brain progranulin expression in rodents. These data will support an additional studies leading to an Investigational Drug Application.