Gene therapy may effectively treat major depression

New York — In a report published in the Oct. 20 issue of Science Translational Medicine, researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center say animal and human data suggest gene therapy to the brain may be able to treat patients with major depression who do not respond to traditional drug treatment.

The researchers hope to rapidly translate their findings into a human clinical trial using the same kind of gene therapy modality the investigators have pioneered to treat Parkinson's disease. A 45-patient randomized blinded phase II multicenter clinical trial using the gene therapy to treat Parkinson's has recently ended and results are being readied for publication.

"Given our findings, we potentially have a novel therapy to target what we now believe is one root cause of human depression," says the study's senior investigator, Dr. Michael Kaplitt, associate professor and vice chairman for research of neurological surgery at Weill Cornell Medical College and a neurosurgeon at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

"Current therapies for depression treat symptoms but not underlying causes, and while that works for many patients, those with advanced depression, or depression that does not respond to medication, could hopefully benefit from our new approach," adds Dr. Kaplitt.

The Science Translational Medicine study demonstrates that a brain protein known as p11 in a single, small brain area, the nucleus accumbens, is critical to the feelings of reward and pleasure that are often missing in depression. This brain region had primarily been studied in addiction research, but the inability to find satisfaction with positive life experiences is one of the major sources of disability in depression.

While investigators believe that depression is a complex disorder that likely involves a number of brain areas and neural circuits, they say their findings suggest that restoring p11 may significantly alter the course of depression in humans.

"Applying molecular neurobiology and gene therapy to depression could dramatically alter the approach to psychiatric diseases," Dr. Kaplitt says. "Our results provide further evidence that the underlying causes of psychiatric disorders are due to molecular changes in key brain circuits, so that they are much more similar to common neurological disorders—such as Parkinson's disease—that might be helped by restoring molecular function."

The study pulls together human and animal data contributed by a team of researchers at NewYork-Presbyterian/Weill Cornell, as well as by investigators at Rockefeller University, Karolinska Institute in Sweden, the University of Texas Southwestern Medical Center and Neurologix in Fort Lee, N.J.