Gene therapy delivered to a specific part of the brain reverses symptoms of depression in a mouse model of the disease — potentially laying the groundwork for a new approach to treating severe cases of human depression in which drugs are ineffective. But the invasive nature of the treatment, and the notorious difficulty in translating neuropsychiatric research from animal models to humans, could complicate its path to the clinic. Many researchers believe that poor signalling of the neurotransmitter serotonin is responsible for causing depression, and common antidepressants act by increasing serotonin's concentration. Research published today in Science Translational Medicine1 uses a virus to deliver an extra dose of the gene p11 to the adult mouse brain. The protein expressed by the gene is thought to bind to serotonin receptor molecules and ferry them to the cell surface, positioning them to receive serotonin's signals from neighbouring cells.
“I think it awakens the possibility of gene therapy for neuropsychiatric diseases,” says Husseini Manji, a senior investigator at Johnson & Johnson Pharmaceutical Research & Development in Titusville, New Jersey, who was not involved in the study. But, he adds, “thinking about delivering a gene to the brain poses all sorts of challenges”.