New antidepressant target discovered
a novel target in the brain using gene therapy could lead to new treatments for
HCN channels reduced depression-like behavior in mice. If replicated in humans,
the findings could inform fresh therapies for millions of patients who do not
respond to existing treatments for depression.
most patients, but they stop working for some patients and don’t work from the
get-go for others,” said senior author Dr. Dane Chetkovich, a professor of
neurology and of physiology at Northwestern University Feinberg School of
Medicine and a Northwestern Medicine neurologist. “There is a real need
for new therapies to help patients desperate for alternatives to the available
|Drugs currently available for treating depression help most patients, but they don’t work for others.|
Most existing antidepressants affect mood and emotions by
increasing levels of neurotransmitters called monoamines, namely serotonin,
dopamine and norepinephrine. But the fact that these drugs are not effective
for many patients suggests there are additional mechanisms underlying
depression yet to be uncovered that could be targeted with new therapies.
those mechanisms might involve the hippocampus, a region of the brain important
for learning, memory and emotional regulation. There, they saw changes to HCN
channels, typically involved in controlling the electrical activity of cells in
the heart and brain, also played a critical role in behaviors linked to
Chetkovich took steps to translate that insight into a potential gene therapy
using mouse models. The scientists surgically injected mice with a nontoxic
virus engineered to express a gene that turns off HCN channel function in hippocampus
behaved as if they’d been given antidepressant medications,” Chetkovich
the antidepressant effect.
how long mice would seek to escape an environment before giving up – a test
commonly used by the pharmaceutical industry to screen compounds for
effectiveness as antidepressants, including medications currently on the
target for depression, it provides a detailed molecular description of the
structures that need to be manipulated for it to act as an antidepressant and
develops viral tools to do so,” said Chetkovich, who is also director of
Feinberg’s Medical Scientist Training Program.
the viral gene therapy approach to human patients. They also have a grant from
the National Institute of Mental Health to find small molecules that could be
developed into oral medications to turn off HCN channels in the brain.
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