Therapeutic delivery of excitatory amino acid transporter for ALS
*Christine Haenggeli, M.D.
Johns Hopkins University, Department of Neurology, Baltimore, MD
(**2004 ALSA POSTDOCTORAL FELLOWSHIP RECIPIENT)

Numerous studies show that glutamate is implicated in neuronal death in acute brain injuries as well as in neurodegenerative diseases such as ALS. Evidence of abnormalities in glutamate handling in ALS comes from the discovery of high extra cellular levels of glutamate in affected brain areas of ALS patients. The increased glutamate levels around vulnerable motor neurons results from a pronounced loss of glutamate transporters present normally on astrocytes, the cells that envelop all motor neurons.  In this proposal we investigate the potential of viral vectors as novel therapeutic tools for ALS to deliver glutamate transporters. Recently we have used adeno-associated virus (AAV) to successfully deliver, through retrograde transport, insulin-growth factor 1 (IGF1) in a mouse model of ALS. By injecting AAV containing the IGF-1 gene peripherally, the disease onset of G93A superoxyde dismutase 1 (SOD1) transgenic mice was significantly delayed and their survival considerably increased. In this proposal we will explore the possibility of using AAV to deliver glutamate excitatory amino-acid transporters (EAATs) to change the disease course of SOD1 mutant mice.