In the not-too-distant future, doctors may use gene therapy to treat severely depressed patients who don't get better with traditional antidepressants.
A team of U.S. and Swedish researchers published a study this week showing that the basic concept works in mice. And now the researchers hope to use their findings as a springboard for launching a human clinical trial.
This promising development is based on years of painstaking work that has shed light on underlying causes of depression.
Neuroscientists have long known that serotonin, a neurotransmitter that conveys messages between brain cells, plays a major role in the disorder. But they weren't sure why serotonin, which normally helps regulate mood, appetite and sleep, doesn't function sufficiently in depressed patients.
Then, in 2007, scientists made a breakthrough in deciphering this mystery. A team, led by Paul Greengard of Rockefeller University, discovered that some depressed patients lack a protein, called p11, in the nucleus accumbens, which is a pleasure-reward centre of the brain. Further studies revealed that p11 is needed to bring serotonin-binding receptors to the surface of nerve cells.
"If the cell does not have these receptors at the surface, it is not capable of properly responding to serotonin," explained one of the researchers, Michael Kaplitt of Weill Cornell Medical College. "P11 is like a tugboat that pulls the receptor to the right position so it can stick out [of the cell]and latch onto the neurotransmitter."
Armed with this fresh insight into the pivotal role performed by p11, the researchers conducted a series of experiments designed to boost levels of the protein in depressed mice. Genes responsible for producing p11 were inserted into deactivated or essentially harmless viruses that were then injected into the nucleus accumbens region of mouse brains.
Just as the researchers had hoped, the viruses entered the brain cells and released their tiny passengers - the p11 genes, which promptly began churning out lots of p11 protein.
Within a short time the depressed, docile and virtually immobile mice seemed to regain their zest for life - as demonstrated by struggling to be free when handled by researchers.
"We didn't just make them better. We essentially cured them," said Dr. Kaplitt, the senior author of the study published in the journal Science Translational Medicine.
Dr. Kaplitt hopes that gene therapy will be equally effective in treating some people who are locked in the grip of depression. He predicts human trials could get started within two years, provided additional animal studies go well.
Of course, there are different forms of depression - not all of which may be linked to abnormal levels of p11. He suspects that the patients most likely to benefit from the treatment would be those whose depression is characterized by anhedonia, or an inability to enjoy normally pleasurable experiences.
Still, it's important to remember that many experimental treatments have produced wondrous results in animal studies, only to fall flat in human trials.Report Typo/Error
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