Michigan team spotlights a new drug target for depression

The FGF9 protein plays a variety of roles in the body, influencing embryonic development, cell survival and tumor growth. But a team of investigators say they have nailed down some convincing animal and tissue data to suggest that in the brain it also could play a key role in depression, offering a new--very complex--target for a disease that afflicts millions.

Investigators from the University of Michigan Medical Center as well as the Pritzker Neuropsychiatric Disorders Research Consortium teamed up to study FGF9. Probing the brain tissue of depressed patients in a post mortem examination and testing their theory in rats, they concluded that lowering levels of FGF9 had a marked impact on anxiety and depression.

The team first elevated levels of the protein by injecting it into the brains of mice, then blocked it with a viral approach using RNAi. Tipping the scales in favor of FGF9 added to symptoms of depression, while blocking it decreased symptoms.

"We call this approach 'reverse translation'," says Huda Akil, a professor of psychiatry. "We start by careful, broad scale analyses in the human brain to discover new molecular players that might play a role in triggering or maintaining the depression. We then follow them up in rodent studies to understand the role of these molecules and determine whether we can target them for new treatments."

Right now the team, which includes doctoral student Elyse Aurbach, is further exploring the role of FGF9 in the brain. As the protein is intricately involved in a variety of functions, the researchers say they have to proceed cautiously in exploring its full potential as a treatment.

Depression drugs have reached a mass audience around the world, but it remains a tough target, subject to disruptively high placebo effects and repeated clinical failures.

- here's the release

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