MEDICATION DEVELOPMENT
Development of more widely effective medications for alcohol-use disorders and organ damage is among NIAAA's highest priorities; it is among the 28 research outcome goals listed in the NIH Government Performance and Results Act report. Medications help prevent or reduce drinking by acting on one or more of the many brain systems through which alcohol exerts its actions. For example, some medications reduce craving for alcohol. We are testing promising compounds for treatment of alcohol-use disorders, by themselves and in combination with behavioral therapies, and for treatment of liver damage.
Recent advances in science and technology have enabled remarkable progress in our understanding of neurobiological mechanisms that underlie behavior, and are revealing new molecular targets for medications for alcohol-use disorders. Likewise, advances in our understanding of organ injury are providing new opportunities for developing medications. These advances are reflected in unprecedented progress in NIAAA's medication development initiative.
A special challenge for our initiative is to develop strategies that will increase translation of promising medications identified by NIAAA research into clinical applications. The pharmaceutical industry has been reluctant to develop medications for alcoholism, and the medical community has been reticent to use new pharmacotherapeutic modalities as an adjunct to traditional behavioral therapies for the treatment of this disease. For example, only 3 to 13 percent of patients treated for alcoholism receive a prescription for the medication naltrexone, although it has yielded positive results in NIAAA-funded studies published in medical journals. We need to increase the likelihood that compounds we identify as effective and safe will reach the market and that they will reach patients who can benefit from them. Research is underway to identify barriers and strategies to remove them.
Our recently established collaboration with the Food and Drug Administration (FDA) will help to expedite progress. Together, NIAAA and FDA are developing standards for clinical trials of medications to be tested as alcoholism treatments. This will help ensure that NIAAA-supported trials are in line with regulatory requirements, enabling them to proceed.
Our two highest priorities for accelerating our medication program are (1) to develop animal models and human research paradigms that can predict the clinical success of potential medications. Having these predictive models in place will prevent spending time and money on more elaborate testing of compounds that would ultimately fail to be effective. (2) Another priority is to establish a network of sites for early stages of human testing of medications, to reveal whether or not a drug should be pursued in larger, more expensive trials. Medications in this system will be on a fast track, in which scientific elements of safety testing, etc., remain, but elimination of unnecessary administrative roadblocks will expedite the process.
IN THE PIPELINE
Human trials of two particularly promising medications are underway. Among the studies being conducted is a collaboration with the National Institute on Drug Abuse (NIDA), to test the antiseizure drug topiramate's effectiveness in treating people addicted to both alcohol and cocaine. Antiseizure drugs act on neurotransmitter systems that modulate brain-cell activity, to restore their natural balance. Alcohol causes an imbalance in the glutamate and GABA neurotransmitter systems (among others) and topiramate's actions on these receptors are thought to ease some of the symptoms of alcohol withdrawal. The drug rimonabant is directed at a different neurotransmitter system (the cannabinoid system) and has shown considerable promise in animal studies. Several other kinds of medications that have shown promise in research settings are in various phases of clinical studies, including several collaborations with other NIH Institutes.
Some populations are at particular risk, and we also are conducting studies specific to them. We are testing medications in youth, who have high rates of alcohol abuse. This group poses special challenges, since the biological changes that occur in the brain during adolescence might compromise the pharmacologic actions of medications used for adults.
People with co-occurring alcoholism and psychiatric conditions are another high-risk group. Our studies of this population include collaborations with the National Institute of Mental Health. In a recent trial, a drug already used as an anticonvulsant and to treat bipolar disorder showed promise in treating alcoholism in bipolar people, who are generally resistant to current medications for alcoholism.
A collaboration with the National Cancer Institute and NIDA is helping researchers to understand the biological interactions that occur between alcohol and nicotine, and to develop treatments for alcoholic smokers. Studies suggest that addiction to alcohol and nicotine involves some common underlying mechanisms.
In addition to developing medications to treat alcohol-use disorders themselves, we are developing treatments for alcoholic liver disease. Alcohol is among the leading causes of death from liver disease in the U.S.
Pharmaceutical companies put aside many of the medications they develop. Even though they may be safe, they may not be optimally effective for treating the diseases or conditions for which they were developed. These medications are potentially useful for treatment of other diseases, and some act on neurotransmitters that we have identified as promising targets for treatment of alcoholism. We are encouraging pharmaceutical companies to collaborate with us in developing these compounds as potential alcoholism treatments.
NEUROSCIENCE AND METABOLISM
The biology of the brain contributes to how we make decisions - to the choices we make in life and the behaviors in which they result. Neuroscience research is essential for understanding the biological basis of alcohol-related behaviors and for identifying molecular targets for therapeutic compounds that can alter alcohol's actions in the brain. Many different biological systems in the brain influence how people respond to alcohol, and chronic, heavy exposure results in brain adaptations that form the underpinnings of alcoholism.
NIAAA-funded scientists are making important discoveries about genes and proteins active in these brain systems, whose variant forms increase or decrease the risk of alcohol-use disorders. For example, recent studies suggest that a gene that produces an appetite-regulating protein fragment, neuropeptide Y, also affects tolerance to alcohol, a predictor of alcoholism and a factor in its development.
In 2006, NIAAA will take part in the NIH Blueprint for Neuroscience, a collaboration of 15 Institutes. We are particularly interested in the Blueprint's cross-training programs for the next generation of researchers and clinicians in neuroscience. One component trains physicians and scientists to work together toward translating neuroscience findings into clinical practice; others provide training in computer and neuroimaging technologies that offer unprecedented research capabilities. The Blueprint's project to target all of the genes in the mouse genome, to discover which of them are critical players in health or diseases of the nervous system, will benefit NIAAA research.
Metabolism also has a profound effect on people's responses to alcohol. Variations in the genes and proteins involved in alcohol metabolism can, like those involved in brain function, increase or decrease risk of alcoholism. NIAAA's metabolism initiative is making progress in identifying these gene/protein variations and their impact on alcohol-related behaviors, particularly in regard to enzymes in alcohol-metabolism pathways. The NIH Roadmap Initiative on National Technology Centers for Networks and Pathways is contributing valuable information to the effort. Like our neuroscience research, our metabolism research is helping us to identify potential targets for therapeutic compounds.
Development of more widely effective medications for alcohol-use disorders and organ damage is among NIAAA's highest priorities; it is among the 28 research outcome goals listed in the NIH Government Performance and Results Act report. Medications help prevent or reduce drinking by acting on one or more of the many brain systems through which alcohol exerts its actions. For example, some medications reduce craving for alcohol. We are testing promising compounds for treatment of alcohol-use disorders, by themselves and in combination with behavioral therapies, and for treatment of liver damage.
Recent advances in science and technology have enabled remarkable progress in our understanding of neurobiological mechanisms that underlie behavior, and are revealing new molecular targets for medications for alcohol-use disorders. Likewise, advances in our understanding of organ injury are providing new opportunities for developing medications. These advances are reflected in unprecedented progress in NIAAA's medication development initiative.
A special challenge for our initiative is to develop strategies that will increase translation of promising medications identified by NIAAA research into clinical applications. The pharmaceutical industry has been reluctant to develop medications for alcoholism, and the medical community has been reticent to use new pharmacotherapeutic modalities as an adjunct to traditional behavioral therapies for the treatment of this disease. For example, only 3 to 13 percent of patients treated for alcoholism receive a prescription for the medication naltrexone, although it has yielded positive results in NIAAA-funded studies published in medical journals. We need to increase the likelihood that compounds we identify as effective and safe will reach the market and that they will reach patients who can benefit from them. Research is underway to identify barriers and strategies to remove them.
Our recently established collaboration with the Food and Drug Administration (FDA) will help to expedite progress. Together, NIAAA and FDA are developing standards for clinical trials of medications to be tested as alcoholism treatments. This will help ensure that NIAAA-supported trials are in line with regulatory requirements, enabling them to proceed.
Our two highest priorities for accelerating our medication program are (1) to develop animal models and human research paradigms that can predict the clinical success of potential medications. Having these predictive models in place will prevent spending time and money on more elaborate testing of compounds that would ultimately fail to be effective. (2) Another priority is to establish a network of sites for early stages of human testing of medications, to reveal whether or not a drug should be pursued in larger, more expensive trials. Medications in this system will be on a fast track, in which scientific elements of safety testing, etc., remain, but elimination of unnecessary administrative roadblocks will expedite the process.
IN THE PIPELINE
Human trials of two particularly promising medications are underway. Among the studies being conducted is a collaboration with the National Institute on Drug Abuse (NIDA), to test the antiseizure drug topiramate's effectiveness in treating people addicted to both alcohol and cocaine. Antiseizure drugs act on neurotransmitter systems that modulate brain-cell activity, to restore their natural balance. Alcohol causes an imbalance in the glutamate and GABA neurotransmitter systems (among others) and topiramate's actions on these receptors are thought to ease some of the symptoms of alcohol withdrawal. The drug rimonabant is directed at a different neurotransmitter system (the cannabinoid system) and has shown considerable promise in animal studies. Several other kinds of medications that have shown promise in research settings are in various phases of clinical studies, including several collaborations with other NIH Institutes.
Some populations are at particular risk, and we also are conducting studies specific to them. We are testing medications in youth, who have high rates of alcohol abuse. This group poses special challenges, since the biological changes that occur in the brain during adolescence might compromise the pharmacologic actions of medications used for adults.
People with co-occurring alcoholism and psychiatric conditions are another high-risk group. Our studies of this population include collaborations with the National Institute of Mental Health. In a recent trial, a drug already used as an anticonvulsant and to treat bipolar disorder showed promise in treating alcoholism in bipolar people, who are generally resistant to current medications for alcoholism.
A collaboration with the National Cancer Institute and NIDA is helping researchers to understand the biological interactions that occur between alcohol and nicotine, and to develop treatments for alcoholic smokers. Studies suggest that addiction to alcohol and nicotine involves some common underlying mechanisms.
In addition to developing medications to treat alcohol-use disorders themselves, we are developing treatments for alcoholic liver disease. Alcohol is among the leading causes of death from liver disease in the U.S.
Pharmaceutical companies put aside many of the medications they develop. Even though they may be safe, they may not be optimally effective for treating the diseases or conditions for which they were developed. These medications are potentially useful for treatment of other diseases, and some act on neurotransmitters that we have identified as promising targets for treatment of alcoholism. We are encouraging pharmaceutical companies to collaborate with us in developing these compounds as potential alcoholism treatments.
NEUROSCIENCE AND METABOLISM
The biology of the brain contributes to how we make decisions - to the choices we make in life and the behaviors in which they result. Neuroscience research is essential for understanding the biological basis of alcohol-related behaviors and for identifying molecular targets for therapeutic compounds that can alter alcohol's actions in the brain. Many different biological systems in the brain influence how people respond to alcohol, and chronic, heavy exposure results in brain adaptations that form the underpinnings of alcoholism.
NIAAA-funded scientists are making important discoveries about genes and proteins active in these brain systems, whose variant forms increase or decrease the risk of alcohol-use disorders. For example, recent studies suggest that a gene that produces an appetite-regulating protein fragment, neuropeptide Y, also affects tolerance to alcohol, a predictor of alcoholism and a factor in its development.
In 2006, NIAAA will take part in the NIH Blueprint for Neuroscience, a collaboration of 15 Institutes. We are particularly interested in the Blueprint's cross-training programs for the next generation of researchers and clinicians in neuroscience. One component trains physicians and scientists to work together toward translating neuroscience findings into clinical practice; others provide training in computer and neuroimaging technologies that offer unprecedented research capabilities. The Blueprint's project to target all of the genes in the mouse genome, to discover which of them are critical players in health or diseases of the nervous system, will benefit NIAAA research.
Metabolism also has a profound effect on people's responses to alcohol. Variations in the genes and proteins involved in alcohol metabolism can, like those involved in brain function, increase or decrease risk of alcoholism. NIAAA's metabolism initiative is making progress in identifying these gene/protein variations and their impact on alcohol-related behaviors, particularly in regard to enzymes in alcohol-metabolism pathways. The NIH Roadmap Initiative on National Technology Centers for Networks and Pathways is contributing valuable information to the effort. Like our neuroscience research, our metabolism research is helping us to identify potential targets for therapeutic compounds.