# A Genetically Modified Skin Graft for Treating Alcohol Use Disorder and/or Polysubstance Abuse With Cocaine

## TL;DR

A genetically modified skin graft was developed to treat alcohol use disorder and cocaine co-abuse by reducing drug-seeking behavior and toxicity.

## Contribution

A novel skin stem cell-based gene delivery platform was developed to treat AUD and polysubstance abuse.

## Key findings

- Production of GLP1 from grafted skin reduced alcohol consumption and dopamine levels in the nucleus accumbens.
- Co-grafting hBChE and GLP1-expressing cells reduced drug-taking and toxicity from alcohol and cocaine.
- Skin grafts may offer a new treatment option for drug abuse and co-abuse.

## Abstract

Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We have developed and used a skin stem cell-based gene delivery platform and found that production of the glucagon-like peptide-1 (GLP1) from the grafted genetically modified skin reduced development and reinstatement of alcohol-induced drug-taking and seeking, voluntary oral alcohol consumption and alcohol-induced increase in dopamine (DA) levels in the nucleus accumbens (NAc). Moreover, we have developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Skin grafts-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by concurrent alcohol and cocaine injections. These results imply that gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.