Gene therapy offers different approach to treating depression

Scientists have shown how manipulating a new target in the brain through gene therapy can lead to new treatments for depression.

By decreasing the function of the HCN channel – a ligand gated ion channel – researchers were able to reduce depression-like behaviour in mice. These channels are usually involved in controlling electrical activity of cells in the heart and brain.

Dr Dane Chetkovich, professor of neurology at Northwestern University in Illinois and senior author, said: “Drugs currently available for treating depression help most patients, but they stop working for some patients and don’t work from the get-go for others. There is a real need for new therapies to help patients desperate for alternatives to the available therapeutic options.”

At the moment, most antidepressants increase neurotransmitters called monoamines, such as serotonin, dopamine and norepinephrine. But they are not effective on all patients, and researchers believe this means there are other chemical reactions responsible for depression that are currently unknown.

The researchers injected mice with a nontoxic virus engineered to express a gene that would switch off the HCN channel function in hippocampus neurons. When the HCN channels stopped working, the mice behaved as if they had been given antidepressants. The effect was reversed when the HCN channel function was increased.

Chetkovich said: “This work not only identifies a totally new treatment target for depression, it also provides a detailed molecular description of the structures that need to be manipulated for it to act as an antidepressant.”

Future research will see the scientists work on adapting this viral gene therapy approach for humans. They are also investigating small molecules that could be developed into oral medications to turn off HCN channels in the brain.

The study was published in Molecular Psychiatry.