VCU researchers identify drug candidate for curbing alcohol misuse – VCU News

Advancing SDG 3: A Report on Novel Therapeutic Approaches for Alcohol Use Disorder

Addressing a Public Health Challenge in Alignment with SDG 3

A Virginia Commonwealth University (VCU) research initiative has identified a potential new treatment for alcohol use disorder, directly contributing to the objectives of Sustainable Development Goal 3 (Good Health and Well-being). The harmful use of alcohol represents a significant barrier to achieving global health targets, and this research explores repurposing an existing drug, tideglusib, to address this critical issue.

• SDG Target 3.5: This research directly supports the goal to strengthen the prevention and treatment of substance abuse, including the harmful use of alcohol.
• Public Health Impact: Alcohol use disorder affects approximately 1 in 10 Americans aged 12 or older.
• Mortality Rates: Excessive alcohol consumption is a leading cause of preventable death in the United States, with alcohol-related deaths having more than doubled in the past two decades. This trend undermines progress toward SDG Target 3.4, which aims to reduce premature mortality from non-communicable diseases.

Current Therapeutic Gaps and the Need for Innovation

While the U.S. Food and Drug Administration has approved three medications for alcohol use disorder (naltrexone, acamprosate, and disulfiram), their efficacy is limited and not universal. This highlights a critical need for new pharmaceutical options, as no new medication has been approved in over 15 years.

Key Limitations of Existing Treatments:

• They are not effective for all patients.
• Long-term effectiveness is a concern.
• Contraindications exist for individuals with specific health conditions, such as kidney or liver problems, or those taking certain medications.

Scientific Discovery and Contribution to Well-being

The VCU research team, led by Dr. Michael F. Miles, focused on the molecular neuroscience of alcohol addiction to identify new therapeutic pathways. Their work contributes to the broader goal of promoting mental health and well-being as outlined in SDG 3.

1. Identification of a Key Protein: Research identified the protein glycogen synthase kinase 3-beta (GSK3β) as being closely linked to drinking behavior. GSK3β is also implicated in other neurological and psychiatric disorders, including Alzheimer’s disease and bipolar disorder.
2. Formulation of a Hypothesis: Previous studies showed that increased GSK3β activity led to increased alcohol consumption in mouse models. The researchers hypothesized that inhibiting GSK3β could decrease alcohol intake.
3. Selection of a Drug Candidate: The team identified tideglusib, a GSK3β inhibitor already in clinical trials for Alzheimer’s disease, as a promising candidate for repurposing.

Preclinical Findings and Future Outlook

The study, published in Addiction Biology, evaluated tideglusib’s effectiveness in preclinical mouse models, with results indicating significant potential for treating problematic alcohol use.

Primary Findings:

• Tideglusib administration significantly reduced alcohol consumption in models of both chronic and binge drinking.
• The drug demonstrated a slightly greater effect in male mice compared to female mice.
• No significant toxicity or adverse side effects were observed during behavioral and biochemical analyses.

These promising results suggest tideglusib is a strong candidate for human clinical trials for alcohol use disorder. The fact that it is already undergoing clinical assessment for other conditions could accelerate its development as a new therapeutic option, directly advancing SDG Target 3.5.

Future Research Directions:

• Investigate the specific brain regions and neurological pathways affected by tideglusib.
• Understand the molecular mechanisms that translate the drug’s effect into reduced drinking behavior.
• Utilize these insights to develop more targeted and effective therapies for substance use disorders.

SDGs Addressed in the Article

The primary Sustainable Development Goal addressed in the article is:

• SDG 3: Good Health and Well-being

  The article directly addresses SDG 3 by focusing on a major public health issue: alcohol misuse and alcohol use disorder (AUD). It highlights the severe health consequences, including its status as a “leading cause of preventable death,” and discusses the development of a new pharmaceutical treatment. The entire research effort described is aimed at improving health outcomes and well-being by providing more effective therapeutic solutions for addiction, which is a core component of ensuring healthy lives.

Specific SDG Targets Identified

Based on the article’s content, the following specific targets under SDG 3 can be identified:

• Target 3.5: Strengthen the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol.

  This target is central to the article. The research on the drug tideglusib is a direct effort to “strengthen the… treatment of substance abuse.” The article explicitly states the need for “more therapeutic solutions for unhealthy alcohol use” and “additional pharmaceutical options for treatment.” The study’s goal to find a drug that can “curb chronic alcohol consumption and binge drinking” directly aligns with addressing the “harmful use of alcohol.”

• Target 3.4: By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.

  The article connects harmful alcohol use to premature mortality and non-communicable diseases. It notes that “excessive alcohol use is one of the leading causes of preventable death” and can lead to “high blood pressure, heart problems, stroke, neuropathy, severe liver disease and cancer.” By developing a treatment for alcohol use disorder, the research contributes to the “prevention and treatment” of these diseases, thereby helping to reduce premature mortality. The article also touches on mental health by noting that the protein GSK3β, targeted by the new drug, is linked to “psychiatric disorders, including Alzheimer’s disease, bipolar disorder, schizophrenia and depression,” thus connecting the research to the promotion of mental well-being.

Indicators for Measuring Progress

The article mentions or implies several indicators that can be used to measure progress towards the identified targets:

1. Indicator for Target 3.5: Coverage of treatment interventions for substance use disorders (Indicator 3.5.1).

   The article implies this indicator by highlighting the limitations of current treatments. It mentions that the three FDA-approved drugs “don’t work for everyone, and they are not as effective in the long term as we would like.” The search for tideglusib as “another therapeutic option” is an effort to improve the coverage and effectiveness of pharmacological interventions for alcohol use disorder.

2. Indicator for Target 3.5: Harmful use of alcohol (Indicator 3.5.2).

   The article provides direct data related to this indicator, stating that “About 1 in 10 Americans ages 12 or older meet the criteria for alcohol use disorder.” The research itself uses the reduction of “chronic and binge drinking levels” in mouse models as a primary measure of the drug’s success, which is a direct proxy for measuring the harmful use of alcohol.

3. Indicator for Target 3.4: Mortality rate attributed to cardiovascular disease, cancer, etc. (Indicator 3.4.1).

   This indicator is clearly implied when the article states that “Americans are more than twice as likely to die from alcohol-related illnesses today than they were 20 years ago.” It also lists the specific non-communicable diseases that contribute to this mortality, such as “heart problems, stroke… and cancer.” Reducing alcohol-related deaths is a direct measure of progress for this indicator.

Summary of SDGs, Targets, and Indicators

Source: news.vcu.edu