$4.8M to Develop New Treatment for Depression
September 02, 2009
UIC News Release
August 18, 2009
CONTACT: Sam Hostettler, (312) 355-2522, samhos@uic.edu
$4.8M GRANT TO DEVELOP NEW TREATMENTS FOR DEPRESSION
The University of Illinois at Chicago has received a five-year, $4.8
million federal grant to develop new therapeutics to treat depression.
Depression, a serious medical illness involving the brain, affects more
than 20 million people in the United States, according to the National
Institute of Mental Health. Symptoms can include sadness, loss of
interest in activities that were once enjoyed, weight change,
difficulty in sleeping (or oversleeping), loss of energy, feelings of
worthlessness and thoughts of death or suicide.
The illness can run in families, and it occurs more often in women than
men. The most common treatment option is the combination of
antidepressant medication and psychotherapy. Other treatments include
lifestyle, behavioral and thought modifications, and alternative and
complimentary medicines.
What's needed are antidepressants that work faster, have fewer side
effects and that act pharmacologically in new ways, says Alan
Kozikowski, UIC professor of medicinal chemistry and pharmacogonosy and
the grant's principal investigator.
Kozikowski and his research team had been designing and synthesizing
novel nicotine-like compounds that target certain receptors in the
brain, in hopes that they would improve cognition in Alzheimer's
disease. Studies in animal models revealed that some of these compounds
had antidepressant activity.
"We thus chose to focus our program on depression, as this offered
a very different target that might lead to something better, with a
faster onset of action," Kozikowski said.
While the main focus of the research now is to develop medications for
depression, Kozikowski said it's likely some candidate compounds may
have other clinical applications, including the treatment of
schizophrenia, pain and nicotine dependence.
In fact, the UIC drug discovery group -- which also includes
investigators from the Barrow Neurological Institute in Phoenix and
from PsychoGenics Inc. in Tarrytown, N.Y. -- has already found that
some of these novel agents do work for pain in animal models.
Prior research has also shown that many smokers smoke to improve their
mood, supporting the notion that nicotine itself has antidepressant
properties. This would explain, Kozikowski said, why cigarette smoking
is much more common among depressed individuals. A recent study found
that smokers are 41 percent more likely than nonsmokers to suffer from
depression.
Such studies suggest that nicotinic compounds that have been modified
to reduce their addictive potential while retaining the ability to
balance mood could provide a new family of antidepressant drugs, he
said.
This new drug class could have greater efficacy and fewer side effects
than antidepressant medications currently on the market that work by
inhibiting monoamine reuptake, Kozikowski said. Side effects of current
antidepressants include headache, nausea, insomnia, dry mouth,
constipation and agitation.
In spite of the intensive efforts that have gone into the design and
study of nicotinic drugs, very few of the compounds have reached
clinical trials, Kozikowski said.
The new grant is part of the National Cooperative for Drug Discovery
and Development Groups and is funded by the National Institute of
Mental Health, one of the National Institutes of Health.
Kozikowski's coworkers include Rong He, research assistant professor at
UIC; Andrew Mesecar, professor in the UIC Center for Pharmaceutical
Biotechnology; Jianhua Liu, postdoctoral research associate at UIC; Ron
Lukas, of the Barrow Neurological Institute; and Barbara Caldarone of
PsychoGenics Inc.