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Researchers May Some Day Treat Depression with Gene Therapy

  • Jessica Berman

Doctors may some day treat patients suffering from major depression with gene therapy. So say scientists who report they are encouraged by human and animal research.

Scientists have identified a protein called p11 in a small region of the brain that plays a role in major depression. The brain region, known as the nucleus accumbens, is responsible for feelings of pleasure and reward.

Researcher Michael Kaplitt of the department of neurological surgery at Presbyterian / Weill Cornell Medical Center in New York, says mice bred without the p11 gene showed signs of severe depression, including passivity when dangled by their tails instead of trying to get away and a disinterest in sugar water, which he says is like candy to mice who normally drink a lot of it.

Kaplitt also says autopsy studies of tissue taken from the brains of people with severe depression showed extremely low levels of p11 in the nucleus accumbens compared to the brains of individuals without depression.

"So if human beings have lower levels of p11 in this area of the brain, if they have depression, and if animals when they have low p11 levels in this area show depression-like behaviors, then that suggests that this might be a very important component of depression; not the only component but it may be a very important component," said Kaplitt.

Using so-called knock-out mice that completely lacked the p11, Kaplitt says researchers inserted a normal copy of the protein into a harmless virus and infused it into the nucleus accumbens of the depressed rodents.

"Now when we restored it to these adult mice, it completely normalized their behaviors; it reversed these depression-like behaviors so that they were back to normal," he said. "So that suggested that if you have low p11 levels in that area, and if that is a cause of depression, that we could potentially reverse it with gene therapy."

Kaplitt and colleagues have also been conducting promising therapy trials with Parkinson's disease patients.

The researchers hope to soon begin gene therapy experiments in patients with major depression who do not respond to anti-depressant medications.

An article on gene therapy for major depression is published in the journal Science Translational Medicine.