$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.





Scripps Research Professors George Koob (top) and Barbara Mason will lead the new Pearson Center for Alcoholism and Addiction Research. Photos by Kevin Fung.