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Gene Therapy for Cocaine Addiction and Cocaine Overdose

Gene therapy is the general term that doctors and scientists use to describe any medical technique that relies on purposeful manipulation of units of DNA inside individual cells, called genes, in order to treat, cure or prevent an illness. Depending on individual circumstances, use of this type of therapy can involve deactivating or switching out an existing gene, or introducing a unique gene not normally found in the body. Currently, researchers are investigating gene-based treatments as a way to treat or prevent cocaine addiction, or to prevent or reverse the effects of a cocaine overdose.

Gene Therapy Basics

Generally speaking, genes are segments or stretches of DNA that produce specific effects when activated inside of a cell. In many cases, activated genes create specialized types of molecules, called proteins, required to support a range of the body’s most basic processes; in other cases, they perform or coordinate additional life-sustaining functions. Each cell in the body contains anywhere from roughly 20,000 to 25,000 individual genes, organized into larger structures called chromosomes. However, only certain genes are active within a given cell or cell type; the function of a cell and its role in human health depends upon the specific genes at work in its interior.

As previously indicated, gene therapy can be used to improve human health in several different ways, including deactivating a defective or mutated gene, replacing a defective or mutated gene with a healthy copy of the same gene, and adding new genetic material that provides a treatment benefit normally provided through such means as surgery or use of conventional medications.

Modification of Neurotransmitter Receptors

Researchers are currently exploring two main avenues of gene therapy for cocaine addiction and cocaine overdose. The first of these avenues involves genetic manipulation of sites called receptors, which sit on the outer surfaces of cells in the brain known as neurons. These neurons form the control and command network required for basic brain communication and coordination, and their receptors help make communication and coordination possible by providing access points for chemicals called neurotransmitters, which carry the messages necessary to turn individual neurons “on” and “off.”

The brain has many different types of receptors, each of which only responds to certain neurotransmitting chemicals. When drugs, medications or alcohol enter the brain, they achieve their effects by effectively mimicking the actions of certain neurotransmitters and activating specific receptor types. In the case of cocaine, the main receptor targets are called dopamine 2 (D2) receptors, which normally respond to the presence of dopamine, a neurotransmitter that plays an important role in the brain by activating the circuits responsible for generating pleasure. In fact, it is cocaine’s ability to highly stimulate the brain’s pleasure circuitry that underlies the drug’s popularity for abuse and addiction.

Because of structural changes triggered by long-term cocaine use, cocaine addicts typically have far fewer D2 receptors in key areas of their brains than people not addicted to the drug. In an animal study published in 2008 in the journal “Synapse,” a multi-institution research team used gene therapy to make specific genetic alterations and increase the numbers of D2 receptors in targeted brain areas of cocaine-addicted rats. Once the numbers of D2 receptors rose in the targeted areas, the researchers saw a significant drop in their test animals’ drug-seeking behaviors. This is critically important, since compulsive drug-seeking is one of the hallmarks of cocaine addiction or any other form of drug addiction.

Modification of Cocaine-Processing Enzymes

In order to break down cocaine and remove the drug from circulation, the human body relies on a specific protein encoded in the genes, called butyrylcholinesterase or BChE; this protein belongs to a large, diverse group of specialized proteins known as enzymes, which collectively support human health in thousands of different ways. Unfortunately, BChE is not particularly effective at breaking down cocaine molecules; for this reason, cocaine easily makes its way to the brain and produces the effects that promote abuse and addiction and, in certain circumstances, also trigger the form of central nervous system poisoning known as a cocaine overdose.

According to a study published in 2008 in the Journal of the American Chemical Society, researchers have discovered a way to use gene therapy to modify the gene that produces BChE inside the body, and thereby make the enzyme both more stable and more powerful. The result of these modifications is a roughly 2,000-fold increase in BChE’s ability to break down cocaine and stop its mind- and body-altering effects. Such rapid activity may prove especially useful for the treatment of an overdose, during which emergency personnel typically need to quickly control cocaine’s harmful effects in order to stop the drug from seriously harming or killing affected individuals.

Considerations

As of 2013, all forms of gene therapy (including gene therapy for cocaine addiction or overdose) are considered experimental, the Mayo Clinic explains, and humans can only access limited types of this treatment by agreeing to participate in a form of testing called a clinical trial. Clinical trials examine the effects of various treatments under controlled circumstances; doctors, public health officials and government agencies then use information from these trials to determine whether or not a given treatment is safe for general use.

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