Adenovirus-mediated transfer of a functional GAD gene into nerve cells: potential for the treatment of neurological diseases

Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter

“…Most animal experiments investigating gene transfer with adenoviral vectors have used viral promoters to drive the transgenes. It would be of interest to test whether the neuronal targeting of therapeutic agents, such as trophic factors, anti-oxidative agents 19 or specific enzymes 20 improves their neuroprotective or restorative effects.…”

Gene therapy in the CNS

“…Exploratory modalities have included: delivery of heat shock protein (HSP72) via an HSV amplicon vector which protect hippocampal neurons from kainic acid toxicity; 200 Ad-mediated delivery of glutamic acid decarboxylase to increase synthesis of the inhibitory neurotransmitter GABA; 240 and lipofectin-mediated delivery of cholecystokinin, an anticonvulsant and anti-opioid neuropeptide, to the ventricles to alleviate (temporarily) audiogenic seizures. 241 Endocrine functions Viral vectors have also been used as tools for examining the role of hormonal replacement therapy in distinct neuroendocrine and/or sensory pathways.…”

Novel targets for CNS gene therapy

“…Among potential gene candidates to consider are those anticipated to reduce the depolarization or synchronization of a focus or its subsequent spreading to downstream networks. 2,3 By taking advantage of the apparent requirement for neural networks to transmit hyperexcitability it is possible to envision a gene therapy that can act locally to disrupt this process. Myriad considerations abound: Which cell types are to be targeted?…”