Study points to possible gene therapy for depression
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Researchers have identified a gene that can cause symptoms of major depression and said it may be possible to use gene therapy to counteract its effects.
They have been testing a similar gene therapy technique in the brains of patients with Parkinson’s disease and may be able to quickly adapt it to depression, Michael Kaplitt of Cornell Medical College and colleagues reported on Wednesday.
“We potentially have a novel therapy to target what we now believe is one root cause of human depression,” Kaplitt, a neurosurgeon, said in a statement.
Depression affects about 121 million people worldwide, according to the World Health Organization, and is diagnosed in at least 13 million U.S. adults each year. It is the main factor in suicide and at least 27 million Americans take antidepressant drugs.
The causes are complex and different patients respond to different treatments.
Kaplitt’s team looked at the activity of a gene called p11 in a part of the brain called the nucleus accumbens.
“This is the center of the brain for reward satisfaction,” Kaplitt said in a telephone interview.
“One of the major problems in depression is what is called anhedonia - an inability to be able to be satisfied or happy or content with normally pleasurable activities in life.”
The p11 gene helps regulate signaling of serotonin, a brain chemical tied to mood, sleep and memory. Many antidepressants target serotonin.
The research team used mice that lacked active p11 and acted depressed.
DEPRESSED MICE
“If you hold a mouse up by its tail, it tends to fight to get away. A mouse showing depressive behavior will just lie there,” Kaplitt said.
Kaplitt’s team has been testing gene therapy for another brain disease, Parkinson’s, in people. They used the same vector - the virus used to carry the new gene into the body - to make a gene therapy replacement for p11.
It transformed the behavior of the depressed mice, they reported in the journal Science Translational Medicine. But taking out a gene and then replacing it in mice does not prove that gene causes human symptoms, or that boosting its production would alter human depression.
So they looked at brain samples taken from people with depression who had died and compared them to samples from people without depression.
Levels of p11 in the nucleus accumbens region - the reward center - were significantly lower in the depressed patients, they found.
Gene therapy for depression is a long way from being tested in people, Kaplitt noted, although he said the Parkinson’s trials show it could be safe.
Gene therapy - replacing or boosting the activity of a faulty gene to correct disease - is still considered highly experimental, although there has been some success in treating forms of blindness and immune deficiency.
“One of the next key steps is to try and test this in non-human primates,” he said. He said his team was collaborating with a team at the National Institute of Mental Health, one of the National Institutes of Health, to test the idea in monkeys.
The study was paid for by the U.S. and Swedish governments as well as private foundations, but Kaplitt has founded a company called Neurologix Inc, which has licensed intellectual property rights to p11 gene therapy for behavioral disorders.
SOURCE: Science Translational Medicine, October 20, 2010.
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