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Ibrutinib utilized as a treatment for cocaine use disorder (CUD) can be used as a neuroprotective effect against cocaine toxicity. According to the National Survey on Drug and Health, almost 1 million people in the United States are affected by CUD and 13% of patients in North American substance-use facilities are treated for CUD. However, there are no current Food and Drug Administration (FDA) approved medications for CUD. Current treatments for CUD rely on behavioral modifications through psychiatric treatment. Clemson University and Emory University researchers have partnered up to uncover the efficacy that Ibrutinib can have in targeting and reversing the expression of cocaine addiction genes in human meso-cortico-limbic circuitry. It additionally has been found to significantly reduce incidence of cocaine-induced seizures. 

Applications:

Cocaine use disorder, Drug addiction, Therapy, Ibrutinib, Repurposed drug development, Biomedical

Technical Summary:

Ibrutinib has been shown to prevent various neurobehavioral and neurotoxic effects of cocaine use. It is a covalent inhibitor of Bruton’s tyrosine kinase and influences intracellular cascades involved in the pro-inflammatory response, Ca+ signaling, and protein kinase activity. These processes are also involved in cocaine use and cocaine-induced seizures. This principle was tested utilizing the Drosophila melanogaster model to evaluate its effects on cocaine-induced phenotypes. The Drosophila dopamine transporter contains a binding site that can accommodate cocaine and exposure to cocaine gives rise to motor responses that resemble behaviors observed in rodents. In addition, flies express an ortholog of Brutons’ tyrosine kinase, BTK29A, in the central brain. Startle behavior and the prevalence of seizure activity was measured in male and female flies following acute consumption of solid food, solid food supplemented with cocaine, or solid food supplemented with cocaine and Ibrutinib. It was observed that both male and female flies that consumed Ibrutinib with cocaine spent more time moving than flies that only consumed cocaine. Male flies that consumed Ibrutinib and cocaine showed a significant decrease in the prevalence of seizures. Fewer cocaine-induced seizures were also observed in Ibrutinib-treated females, but this observation did not reach statistical significance since the incidence of cocaine-induced seizures was lower in females than in males. 

Advantages:

  • Acts on central brain structures, counteracting neurological pathways for CUD seizures and addictiveness. 
  • Reverses patterns of cocaine gene expression, allowing for CUD psychosocial intervention techniques to become more effective. 
  • Ibrutinib is already an FDA-approved medication for chronic lymphocytic leukemia, making it an optimal option for CUD treatment, which currently has no FDA-approved medication. 

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Technology Overview

State of Development

Proof of Principle

Patent Type

N/A

Category

Biomedical

Serial Number

63/071,596

CURF Reference No.

2022-008

Inventors

Robert Anholt and Trudy Mackay


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