Gene Therapy for Depression

A gene injected into one region of the brain might hold the key to treating depressed patients who fail to respond to conventional therapies.

Writing in Science Translation Medicine, Cornell-based scientist Brian Alexander and his colleagues show how manipulating a gene called p11 in a brain region known as the nucleus accumbens can alter behaviour.

Mice genetically engineered to lack the gene, which plays a role in sensitising nerve cells to serotonin, one of the brain's feel-good nerve transmitter chemicals, display behaviours consistent with depression, including a lack of interest activities that control animals find rewarding. But, by using a modified adeno-associated virus as a vector to add the gene back into the nucleus accumbens, which is known to be the brain's main pleasure centre, the team found that the previously p11-deficient mice began to behave like their normal control counterparts.

Intriguingly, brains from depressed humans studied post mortem show that the human p11 gene is also present at much lower levels in the same brain regions of these subjects, suggesting that what works in the mice might also work in man. And as clinical trials are already underway in patients with Parkinson's Disease to add therapeutic genes that can remedy some of the symptoms of the disorder, the same techniques could be used to deliver extra copies of p11 to depressed people.

But, in the nearer term, researchers will also now focus on finding other ways to manipulate the activity of the p11 gene, which could offer a range of new ways to fight depression.