Gene therapy could become a powerful new weapon in the fight against severe depression that does not respond to traditional drug treatments, US researchers said Wednesday.
Restoring a key gene that activates a specific protein in the tiny part of the brain known as the nucleus accumbens reversed depression-like behavior in mice, the researchers said in the latest issue of Science Translational Medicine.
"Given our findings, we potentially have a novel therapy to target what we now believe is one root cause of human depression," said lead researcher Michael Kaplitt, a neurosurgeon at New York Presbyterian Hospital.
"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," he added.
The research found that a particular protein known as p11 in the nucleus accumbens was associated with experiencing pleasure and a sense of satisfaction that is often absent in severe depression.
Postmortem analysis on human subjects revealed that people with severe depression had low levels of the p11 protein compared to more normal subjects.
In their studies, mice without p11 all exhibited depression-like behaviors, researchers said, leading the team to suggest that restoring this function and the availability of p11 was critical to alleviating depressive symptoms.
"In the absence of p11, a neuron can produce all the serotonin receptors it needs, but they will not be transported to the cell surface," said Kaplitt.
Serotonin is needed to transmit impulses, or informative data, between neurons and between neurons and other parts of the brain.
The therapy would insert a manufactured virus into the brain cells to deposit "a genetic payload" into the genome of neurons that would produce the protein, according to the research.
"Together, these studies provide strong evidence that maintaining adequate levels of this particular protein, p11, in this pleasure-reward area of the brain may be central to preventing or treating depression," Kaplitt said.