(Embargoed for release at 2 p.m./1800 GMT)
* p11 gene under-active in brains of depression patients
* Replacing p11 in mice reversed symptoms
* Tests in human patients years away
By Maggie Fox, Health and Science Editor
WASHINGTON, Oct 20 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
The causes are complex and different patients respond to
Kaplitt's team was looking at 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
They used mice lacking active p11, which act depressed.
"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 -- was significantly lower in the depressed patients,
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 NRGX.OB, which has licensed
intellectual property rights to p11 gene therapy for behavioral