$3 Million Donation Establishes Pearson Center for Alcoholism
and Addiction Research
By Keith McKeown
and Jason Socrates Bardi
The Scripps Research Institute recently received a $3 million
gift to establish The Pearson Center for Alcoholism and Addiction
Research that will combine biomedical research with clinical
application to fight this deadly and costly disease.
The donor, who wishes to remain anonymous, stated that the
gift is "in memory of my parents whom I lost to alcoholism
and addiction and on behalf of other family members and friends
who have suffered, directly or indirectly, from the devastating
consequences of this disease. It is my hope that by generating
greater public awareness and additional financial support
for biomedical and clinical research, future generations of
families will be spared from the devastating affects of this
disease."
"We are very grateful for this extraordinary donation, "
said Scripps Research President Richard A. Lerner. "Scripps
is in a unique position to fulfill the donor's wish that biomedical
research on alcoholism and addiction be translated into testing
treatments to curb addiction and relapse."
In leading the center, Professor George F. Koob will collaborate
with Professor Barbara Mason. Koob directs the Division of
Psychopharmacology of the Scripps Research Department of Neuropharmacology
and Mason directs its Division of Clinical Pharmacology.
A New Approach to Treating Alcoholism
"Alcoholism is a disease of the spirit, of behavior, and
also of the brain," said Mason, who adds that the brain is
often overlooked in treatment.
The traditional mode of treatment involves group therapy
and other forms of psychological counseling that aim to empower
the spirit and address the destructive behaviors associated
with alcoholism. These are important approaches, however,
the center will seek to complement them through the development
of new medications to treat alcoholism—particularly drugs
to help prevent relapse.
Prospects for enhancing traditional treatment through pharmaceuticals
have never been more promising, and work at Scripps Research
and elsewhere has already highlighted some of the key changes
in the brain that occur when a person transitions from social
drinking to alcohol abuse and dependence. By further researching
these changes, the center's scientists hope to develop compounds
that will assist in normalizing the brain during an alcoholic's
recovery.
Particularly, the researchers will focus on the physiological
changes in the brain that drive excessive drinking and create
vulnerability to relapse. Specifically, the researchers will
study the viability of utilizing new compounds, designed at
Scripps Research or elsewhere, to modulate the neurological
effects of alcohol and reduce excessive intake or relapse.
"Once we know the circuits and the basis for alcoholism,
we can develop new targeted treatments," says Koob. "There
are a number of possible neurotransmitter candidates to focus
on."
One of these, called gamma amino butyric acid (GABA), is
the main inhibitory neurotransmitter in the brain. Alcohol
produces many of its intoxicating actions through facilitation
of GABA receptor function, and preclinical studies of alcohol
dependence at Scripps Research have shown that GABAergic activity
decreases during alcohol withdrawal and protracted abstinence.
Another target for therapy at the center will be the brain
corticotropin releasing factor (CRF) stress system— which
is responsible for activating the pituitary adrenal stress
response and is one of the major neurotransmitters responsible
for activating sympathetic and behavioral responses to stressors.
The CRF system seems to be central to alcoholism, and preliminary
results in preclinical studies at Scripps Research have shown
that compounds known as CRF antagonists can block the excessive
drinking associated with alcohol withdrawal and protracted
abstinence.
The center will aim to discover and test new CRF antagonists
and other compounds that might be translated into new and
practical treatments for alcoholism that can assist in recovery.
The center will also aim to bring these compounds rapidly
to clinical trials.
The center's private funding will enable the researchers
themselves to determine how best to direct their efforts.
The center will maximize the effectiveness of the funding
by attracting additional public and private grants to conduct
research on alcoholism and the brain.
Center to Build on Scripps' History of Addiction Research
The center will benefit both from Mason's experience in
conducting clinical trials and Koob's expertise in neuropharmacology
and preclinical research.
Since the 1970s, Koob and other Scripps Research scientists
have received numerous grants and awards and are recognized
for their work in the science of alcoholism, addiction, and
the brain.
Scripps Research investigators identified a large part of
the neurocircuitry that is involved in the reinforcing action
of alcohol, and they have begun to identify how this circuitry
changes when a person becomes an alcoholic. They also established
several working laboratory models that mimic the transition
from social drinking to dependence and that are useful for
pre-clinical studies on the efficacy of a potential therapeutics.
In recent years, Koob and other researchers at Scripps have
begun to collaborate with clinicians like Mason to turn some
of these observations into new therapies. In fact, it was
just such a collaboration between Mason and Koob that led
Mason to Scripps Research in the first place. She joined the
institute from the University of Miami School of Medicine
in June 2003 after a successful collaboration on a research
grant.
Mason has extensive experience conducting clinical trials
related to alcohol addiction. In 1999, Mason and her colleagues
at the University of Miami conducted a 12-week placebo-controlled
clinical trial on a compound called nalmefene, which proved
effective at preventing relapse to heavy drinking in alcohol-dependent
individuals. Patients who received nalmefene were 2.4 times
less likely to relapse to heavy drinking than those who received
a placebo.
Mason was also the principal researcher on a clinical trial
of a second abstinence-prolonging compound called acamprosate,
which she studied with her colleagues at the University of
Miami. Based on the promising results of the trial, which
was conducted in 21 cities nationwide, acamprosate is in the
U.S. Food and Drug Administration approval process and could
become available shortly in this country.
At Scripps Research, Mason has just begun a study on gabapentin,
an anti-convulsant that has been successful in controlling
bipolar states, anxiety, and agitation. The compound, Mason
says, may work like acamprosate to address the debilitating
mood and sleep disturbances suffered by alcoholics.
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