Penn Awarded $1.8 Million to Search for New Mood-Disorder
in a Collaboration With Wyeth Research Laboratories
(Philadelphia, PA) - The National Institute of Mental Health (NIMH) has
awarded the University of Pennsylvania School of Medicine
$1.8 million over the next three years to establish a National Cooperative
Drug Discovery Group for the Treatment of Mood Disorders (NCDDG-MD). This
group is comprised of researchers from the Center for Neurobiology at
Penn and the Neuroscience Discovery Department at Wyeth Research Laboratories,
Princeton N.J. The aim of this National Institutes of Health (NIH)-sponsored
academic-industry collaboration is to develop new antidepressant drug
treatments based on the role of neurogenesis (the production of new neurons)
in regulating stress and depression.
“The NIH wants drug-development programs to jump-start new approaches
for creating drugs to treat depression,” explains Irwin
Lucki, PhD, Professor of Psychiatry and principal investigator
of the Penn component of NCDDG-MD.
The Wyeth component is led by Lee Schechter, PhD, who is the Therapeutic
Area Head for Depression and Anxiety Research in Neuroscience Discovery.
“The previous research findings demonstrating that antidepressants
can induce neurogenesis in the brain has opened up a new and exciting
area for scientific investigation delving into novel mechanisms of antidepressant
drug action,” says Schechter. “We are very excited about this
initiative with Penn under the NCDDG-MD program.”
According to the World Health Organization (WHO), approximately 121 million
people currently suffer from depression, which can lead to reduced productivity
in the workplace and home. “Depression causes immense financial
burdens for individuals and their families, as well as society,”
echoes Lucki. WHO estimates that the annual costs of mental illness in
the U.S. is close to $148 billion. Although effective treatments for depression
do exist, they are marked by limitations, such as side effects and a three-to-five-week
delay before they take effect. And, less than 60 percent of patients seeking
treatment respond to current antidepressants.
In recent years, advances in imaging techniques have allowed researchers
to scan the brains of patients suffering from depression. Such brain images
show distinct shrinkage in the hippocampus and cortex, regions known to
play a role in mediating mood and cognitive reasoning. Animal studies
reveal that chronic stress leads to similar volume and cell loss in these
brain regions, suggesting a link between depression and stress throughout
“Increasingly, we are learning that certain areas of the brain are
responsible for generating new cells, and this renewal process is causing
us to reexamine the way that stress affects the brain,” explains
Lucki. Stress reduces the amount of neurogenesis, or cell growth, in these
areas of renewal. Conversely, chronic administration of antidepressant
drugs increases neurogenesis. The NCDDG-MD is in the midst of identifying
compounds that facilitate neurogenesis in key areas of the brain to develop
innovative therapies for depression.
Recently, Penn and Wyeth researchers examined a hormone called insulin-like
growth factor (IGF-1) that has been shown to promote neurogenesis. Brian
Hoshaw, PhD, research associate in the Department of Psychiatry at Penn,
in collaboration with Jessica Malberg, PhD, Senior Research Scientist
in Neuroscience Discovery at Wyeth, discovered that IGF-1 produces behavioral
effects similar to antidepressant treatments in animal models. With further
examination of the way that IGF-1 and other neurotrophins increase neurogenesis,
the research team may be able to develop better antidepressant drugs.
The NCDDG-MD is also developing an animal model capable of detecting the
effects of antidepressants on chronic stress using neurogenesis. With
such a model, researchers could begin to better understand the delay in
drug efficacy of antidepressants and how this may relate to changes in
neurogenesis, suggest Lucki and Schechter.
Lucki, Hoshaw, and Penn colleagues state no financial interests in Wyeth.
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