Gene therapy involves replacing or altering a small part of DNA whose abnormal expression causes a disease. The new therapeutic technique has shown promise for the treatment of cystic fibrosis, hemophilia and muscular dystrophy. Now, according to scientists at Weill Cornell Medical Center, perhaps depression should be added to this list as well.
That’s the suggestion made by Michael Kaplitt and colleagues in their write-up summarizing the results of their recent experiments which appears in Science Translational Medicine.
Kaplitt’s team knew that abnormalities in a particular region of the brain-the nucleus accumbens-were associated with depression in humans and behaviors akin to depression in mice (specifically, murine responses to rewards and pleasurable experiences). They knew that the problem in the nucleus accumbens had to do with abnormalities in the way the neurotransmitter serotonin impacted chemical pathways that mediated mood, appetite and sleep patterns. And they knew that most antidepressant drugs acted to regulate serotonin metabolism in the brain.
Kaplitt’s group went from there to isolate the problem with serotonin metabolism in the nucleus accumbens of “depressed” mice. It turned out to be the lack of a single protein, known as p11, which normally serves to transport serotonin receptors to the surface of nerve cells. When p11 was missing or didn’t work properly, nerve cells could produce adequate amounts of serotonin receptors, but the receptors never made it to the surface of the nerve cell membrane where they could bind serotonin and thus trigger normal behavioral responses.
Kaplitt’s team then used somatic gene transfer (that is, “gene therapy”) to replace the gene responsible for producing the defective p11 protein in the nucleus accumbens of their depressed mice. They subsequently observed that the depressive symptoms disappeared.
“We potentially have a novel therapy to target what we now believe is one root cause of human depression,” Kaplitt told BurrillReport. Kaplitt’s team hopes to launch a clinical trial of gene therapy in humans with depression sometime soon.