Gene Therapy for Cocaine Use Disorder

Overseen by Michael Hooten, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: W. Michael Hooten

Disqualifiers: HIV, Hepatitis, Pregnancy, Morbid obesity, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment that uses a virus to deliver a gene helping to break down cocaine. It targets adults who have had cocaine use disorder but are currently in remission. The treatment works by producing an enzyme that reduces the pleasurable effects of cocaine.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to get a clear answer.

What data supports the effectiveness of the treatment AAV8-hCocH for cocaine use disorder?

Research shows that the AAV8-hCocH treatment, which uses a viral vector to deliver a gene that breaks down cocaine, is safe and effective in mice. Mice treated with this therapy had less tissue damage from cocaine use, suggesting it could help reduce cocaine's harmful effects. ^{1 2 3 4 5}

Is the gene therapy AAV8-hCocH safe for humans?

Studies in mice show that the gene therapy AAV8-hCocH is safe, with no harmful effects observed. It was well tolerated, and even protected against some cocaine-related damage, suggesting it could be safe for humans too. ^{1 2 5 6 7}

How is the treatment AAV8-hCocH for cocaine use disorder different from other treatments?

AAV8-hCocH is a unique gene therapy that uses a viral vector to deliver a modified enzyme into the body, which breaks down cocaine into harmless substances, reducing its effects and potential for addiction. Unlike traditional treatments, this approach directly targets the metabolism of cocaine, offering a novel method to help individuals remain abstinent. ^{1 4 5 7 8}

Research Team

Michael Hooten, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults aged 18-65 with a diagnosis of cocaine use disorder in remission can join this trial. They must be motivated to stay off cocaine, able to attend regular clinic visits, and have normal heart rhythms and general health. Pregnant or breastfeeding individuals, those with obesity (BMI > 40), immunity to AAV8 capsid, HIV/hepatitis, kidney issues (Creatinine ≥ 1.5 mg/dL), or other disqualifying conditions cannot participate.

Inclusion Criteria

DSM-5 diagnosis of cocaine use disorder in sustained remission as confirmed by the PI's review of the medical record

Show a baseline EKG that demonstrates normal sinus rhythm and conduction without clinically significant abnormalities or arrhythmias

I am between 18 and 65 years old and not currently seeking treatment.

Exclusion Criteria

Any disease or mental health condition at the physician's discretion that would prevent the subject from fully complying with the requirements of the study. The physician may exclude subjects with active alcohol abuse, other substance abuse or positive urine toxicology screen for substances of abuse

I am not pregnant or breastfeeding and agree to use birth control during the study.

My BMI is over 40.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time IV administration of AAV8-hCocH at varying dose levels

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and enzyme expression levels after treatment

7 weeks

Multiple visits (in-person)

Long-term follow-up

Participants are monitored for long-term safety and effectiveness

24 months

Treatment Details

Interventions

• AAV8-hCocH (Virus Therapy)

Trial Overview The trial is testing a new gene therapy using AAV8-hCocH for adults who are not seeking treatment but want to maintain their remission from cocaine use. This gene helps break down cocaine quickly which may reduce its pleasurable effects.

Participant Groups

Group I: AAV8-hCocH dose level 3: 6e12vg/kg Experimental Treatment 1 Intervention

Cohort 3: Participant receives one-time IV administration of medium dose 6e12vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Group II: AAV8-hCocH dose level 2: 4e12vg/kg Experimental Treatment 1 Intervention

Cohort 2: Participant receives one-time IV administration of medium dose 4e12vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Group III: AAV8-hCocH dose level 1: 2e12 vg/kg Experimental Treatment 1 Intervention

Cohort 1: Participant receives one-time IV administration of low dose 2e12 vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Who Is Running the Clinical Trial?

W. Michael Hooten

Lead Sponsor

Trials

1

Recruited

10+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

Findings from Research

AAV8-hCocH gene therapy, which uses a viral vector to help metabolize cocaine into harmless by-products, showed no adverse effects in both cocaine-experienced and naive mice, indicating a strong safety profile for this treatment approach.

Mice treated with AAV8-hCocH had significantly less tissue damage compared to those that received cocaine without the gene therapy, suggesting that this method could effectively reduce the harmful effects of cocaine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Safety of a Recombinant AAV8 Vector for Human Cocaine Hydrolase Gene Therapy: A Good Laboratory Practice Preclinical Study in Mice. Chen, VP., Gao, Y., Geng, L., et al.[2021]

Gene transfer of a cocaine-hydrolyzing enzyme (CocE) significantly reduced cocaine's effects in brain reward centers, as shown by a 25,000-fold increase in cocaine hydrolase activity after intravenous delivery in rats.

Rats treated with the active CocE vector showed minimal FosB expression in response to cocaine, indicating a protective effect against cocaine-induced changes, similar to rats that had never been exposed to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lasting reduction of cocaine action in neostriatum--a hydrolase gene therapy approach. Gao, Y., Brimijoin, S.[2021]

Transplanting skin cells modified to produce an enhanced form of butyrylcholinesterase in mice significantly reduces cocaine-seeking behavior and protects against cocaine overdose, suggesting a novel approach to treating cocaine addiction.

This study highlights the potential of cutaneous gene therapy as a long-term solution for drug abuse by enabling the body to eliminate cocaine more effectively, marking a promising direction for future therapeutic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose. Li, Y., Kong, Q., Yue, J., et al.[2023]

Engineered versions of human butyrylcholinesterase (BChE) can effectively break down cocaine in the bloodstream, reducing its effects on the brain and diminishing addictive behaviors.

Advancements in anti-cocaine antibodies and vaccines, combined with gene transfer methods for delivering these treatments, show promise for addressing cocaine addiction, though potential risks must be carefully considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interception of cocaine by enzyme or antibody delivered with viral gene transfer: a novel strategy for preventing relapse in recovering drug users. Brimijoin, S.[2021]

Site-directed mutagenesis has created new enzymes that can rapidly break down cocaine, and researchers are exploring the potential of using gene therapy to deliver these enzymes directly to the brain to reduce cocaine's effects and addiction risk.

In a study where vectors were injected into the nucleus accumbens of rats, significant increases in cocaine-hydrolyzing enzyme activity were observed, suggesting that this method could effectively limit cocaine's access to the brain and support future addiction treatment research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viral transduction of cocaine hydrolase in brain reward centers. Gao, Y., Brimijoin, S.[2019]

In a study involving mice treated with high doses of cocaine, pretreatment with a viral vector delivering cocaine hydrolase effectively protected against cocaine-induced prolongation of the QT interval, a serious heart condition.

The viral delivery of cocaine hydrolase showed no intrinsic cardiac toxicity, indicating it is a safe therapeutic option for mitigating the cardiac risks associated with cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cocaine Hydrolase Gene Transfer Demonstrates Cardiac Safety and Efficacy against Cocaine-Induced QT Prolongation in Mice. Murthy, V., Reyes, S., Geng, L., et al.[2018]

In a study involving mice, gene transfer of human butyrylcholinesterase (BChE) using viral vectors showed no adverse physiological or metabolic effects, even at high doses, indicating a strong safety profile for this potential therapy.

The treatment not only maintained normal physiological parameters but also protected the mice from the negative effects of cocaine, suggesting that BChE gene therapy could be a promising approach for treating cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologic and metabolic safety of butyrylcholinesterase gene therapy in mice. Murthy, V., Gao, Y., Geng, L., et al.[2021]

Gene transfer of a modified mouse cocaine hydrolase (mCocH) showed a significant increase in enzyme activity and sustained expression in mice for over a year without triggering an immune response, indicating its potential for treating cocaine addiction.

The advanced viral vector used for gene transfer not only enhanced cocaine hydrolase activity dramatically but also protected mice from severe behavioral and physiological effects of cocaine overdose, suggesting a promising therapeutic approach for addiction management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene transfer of mutant mouse cholinesterase provides high lifetime expression and reduced cocaine responses with no evident toxicity. Geng, L., Gao, Y., Chen, X., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Systemic Safety of a Recombinant AAV8 Vector for Human Cocaine Hydrolase Gene Therapy: A Good Laboratory Practice Preclinical Study in Mice. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Lasting reduction of cocaine action in neostriatum--a hydrolase gene therapy approach. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose. [2023]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Interception of cocaine by enzyme or antibody delivered with viral gene transfer: a novel strategy for preventing relapse in recovering drug users. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Viral transduction of cocaine hydrolase in brain reward centers. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Cocaine Hydrolase Gene Transfer Demonstrates Cardiac Safety and Efficacy against Cocaine-Induced QT Prolongation in Mice. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Physiologic and metabolic safety of butyrylcholinesterase gene therapy in mice. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Gene transfer of mutant mouse cholinesterase provides high lifetime expression and reduced cocaine responses with no evident toxicity. [2021]