Monday, June 02, 2008

Drugs to Grow Your Brain

Compounds that trigger the growth of new brain cells might help treat depression.

By Emily Singer

Newborn neurons: This image shows a section of the hippocampus, the part of the brain important for learning and memory. Mature neurons are shown in green, while newborn neurons are orange, and neural stem cells are red. Credit: BrainCells Inc.

Drugs that encourage the growth of new neurons in the brain are now headed for clinical trials. The drugs, which have already shown success in alleviating symptoms of depression and boosting memory in animal models, are being developed by BrainCells, a San Diego-based start-up that screens drugs for their brain-growing power. The company hopes the compounds will provide an alternative to existing antidepressants and says they may also prove effective in treating cognitive disorders, such as Alzheimer's.

"The fact that you might be able to take small molecules to stimulate specific cells to regenerate in the brain is paradigm-shifting," says Christopher Eckman, a neuroscientist at the Mayo Clinic in Jacksonville, FL. "[This approach] takes advantage of the body's innate ability to correct itself when given appropriate cues." Eckman studies compounds that boost brain cell growth in models of neurodegenerative disease and is not involved with BrainCells.

In the last ten years, scientists have discovered that new neurons are born in the adult brain and that increases or decreases in this cell growth, known as neurogenesis, may be involved in myriad brain diseases, including depression, schizophrenia and stroke. Subsequent research has shown that existing drugs, including Prozac and other antidepressants, boost neurogenesis. In fact, that property may be an integral component of the drugs' effectiveness--for example; some experiments suggest that new cell growth in the hippocampus is necessary for antidepressants to work.

Scientists at BrainCells aim to exploit that finding by screening drugs expressly for their ability to boost brain cell growth. (While some existing drugs have this effect, they weren't selected for it.) Scientists select drug candidates by assessing their impact on human neural stem cells growing in a dish, examining how many new cells are born and how well they develop into fully differentiated neurons. The company is focusing mainly on drugs that are already on the market or have been tested in humans for other indications and therefore have a good safety profile.

After screening different types of antidepressant compounds that are already on the market, researchers at BrainCells found all the drugs have a similar ability to boost brain cell growth. However, existing antidepressants fail to help 30 to 50 percent of patients and often carry problematic side-effects. So the scientists began searching for other compounds that carry similar benefits but lack the side effects. "It's possibly that some people who don't respond to SSRIs [a common type of antidepressant] would respond to a drug that targets neurogenesis directly," says James Schoeneck, Braincells's chief executive officer.