Gene therapy effectiveness differs for neuronal survival and behavioral performance

If neuronal gene therapy is to be clinically useful, it is necessary to dem onstrate neuroprotection when the gene is introduced after insult. We now r eport equivalent neuronal protection if calbindin D-28K gene transfer via h erpes simplex virus amplicon vector occurs immediately, 30 min, or Ih after an excitotoxic insult, but not after a 4h delay. Behavioral performance wa s evaluated for immediate and Ih delay groups using a hippocampal-dependent task. Despite equivalent magnitude and pattern of sparing of neurons with the immediate and 1 h delay approaches, the delay animals took a significan tly longer time after insult to return to normal performance.