Gene therapy eased symptoms of depression in a mouse study that may spur new research in humans, scientists said.
The researchers studied mice that acted depressed and lacked a protein, called p11, thought to play a role in brain function. When the authors injected a gene into the animals’ brains that produced the protein, they behaved normally, said a report in the journal Science Translational Medicine.
If the therapy also works in an ongoing study in monkeys, the researchers said they would seek approval to test it in people within a year or two. Gene therapies have shown success in treating Parkinson’s disease and brain and eye disorders. This would be the first human test of a gene therapy in a psychiatric condition with an known cause.
“The use of gene therapy to treat complex psychiatrist diseases represents uncharted territory,” said Husseini Manji, the neuroscientist, and two colleagues from Johnson & Johnson, the New Brunswick, New Jersey-based drugmaker, in a commentary that accompanied the study.
Human testing must be approved by an oversight committee for research at universities and this therapy is likely to face resistance, said David Antonuccio, a psychologist and professor of psychiatry and behavioral sciences at the University of Nevada School of Medicine in Reno.
“My worry would be for the unintended and unexpected consequences of altering genes in humans,” Antonuccio said in an e-mail. “With drug research, at least the drug can be stopped.”
Urgent Need
Still, an urgent need exists to find a better treatment for depression, said Michael Kaplitt, a neurosurgeon at New York- Presbyterian Hospital/Weill Cornell Medical Center in New York, who led the experiment, in a telephone interview yesterday.
“I think it would be a major mistake to prevent this treatment from moving forward,” said Kaplitt, a founder and shareholder of Neurologix Inc., a Fort Lee, New Jersey, company that has licensed the rights to the gene therapy used in the trial. “Major depression is one of the most prevalent diseases in the world and one of the major causes of lost work time.”
The experimental therapy builds on the research of Paul Greengard, a professor at Rockefeller University in New York who won the Nobel Prize in physiology and medicine in 2000 for work on how brain chemicals, called neurotransmitters, aid communication between nerve cells in the brain.
Serotonin in Depression
In 2006, Greengard and his colleagues reported that a protein called p11 enables neuron receptors to connect with a neurotransmitter called serotonin. Serotonin is thought to be involved in depression and is the brain chemical that antidepressants like Eli Lilly & Co.’s Prozac attempt to boost.
Greengard is a founder and shareholder in Intra-Cellular Therapies Inc., a closely held company based in New York that has licensed patents for p11. He and Kaplitt collaborated on the research and were the senior authors of today’s paper.
If people have too little p11, it may help explain why they’re depressed and why antidepressants don’t help them, Kaplitt said in a telephone interview yesterday.
The mice in the study were given two tests often used to measure depression and the effects of antidepressant drugs. The mice stopped struggling more quickly than normal when they were held upside down by their tails, or put in a water tank from which they couldn’t escape.
Rat pups bred to have no p11 had the protein injected into their brains when they were two days old. After recovering from the injection, they were seen to struggle longer. They also displayed more interest in sugar than the other mice, suggesting they had more interest in pleasure.
Brains of the Dead
To assess human evidence, Kaplitt and his colleagues examined the brains of depressed and nondepressed people who had died. Looking at a region called the nucleus accumbens, often described as the brain’s pleasure center, they found low levels of p11 in those who had suffered from depression and higher levels in those hadn’t.
Concluding that low p11 caused the patients’ depression is making an unwarranted leap, said Antonuccio, the psychiatry professor. The low p11 levels could be a result of the patients’ depression as easily as a cause of it, he said.
“That is the problem with most correlational results,” he said yesterday in an e-mail. “Correlation does not mean causation.”
The research was funded by grants from the U.S. Department of Defense, the National Institutes of Health and two foundations.
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