Is Alcoholism a disease, which can be treated?

Alcohol use disorders (AUDs) have great national effects that influence over 18 million people and is responsible for over 100,000 deaths in the United States. Few therapeutic options urge to introduce better effectual treatment. Dr. Kelle M. Franklin and his team from Indiana University School of Medicine have found the relationship between the P2X4 receptor (P2X4Rs) and ethanol consumption and suggested a potential clinical use of ivermectin (IVM) for the treatment of AUDs. P2XR is known mostly as abundant ligand-gated ion channels (LGICs) in the CNS. The ion channel is controlled by extracellular ATP activation and influences important cellular mechanisms such as neurotransmission and hormones secretion. The study demonstrated that animal models with lower functional expression of the P2RX4 gene showed more alcohol preference than others with the higher functional expression of the gene. As a result, the experimental group of mice lacking the gene drank more ethanol containing beverages than the wild type controls. Other wise, IVM has a positive effect as a modulator of P2X4Rs in order to antagonize the ethanol-mediated inhibition of P2X4Rs in vitro. As a result, it reduces the tendency of ethanol intake in vivo.

Most treatment of AUDs attempt to block metabolism of alcohol intake or to enhance neurochemical and neuropeptide systems for craving and dependence. However, the field is still relatively new and there is still much progress to be made. The study has suggested that IVM would be a potential clinical tool for AUDs. IVM is already approved by the FDA in the use of veterinary and clinical medicine. IVM regulates a number of ion channels in terms of enhancing inhibitory neurotransmission and reducing excitatory transmission. So, the agonistic effect of IVM proposes to block P2X4Rs pathway and eventually reduce the alcohol intake behavior of patients.

As in the case of all animal researches, animal models cannot be used to fully cover a human. The P2X4R used in the study was cultured from rats. In the human body, hP2X4 mostly corresponds to the specific gene from a rat and it shares about 87% of the rat polypeptide sequence. It is uncertain whether the finding would coincide within human beings as it had been studied within only animal models. Still, 13% of the difference in gene sequence remains a relatively large difference in terms of genetics.

 Reference

Franklin, K. M., Asatryan, L., Jakowec, M. W., Trudell, J. R., Bell, R. L., & Davies, D. L. (2014). P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders. Front Neurosci, 8, 176. doi: 10.3389/fnins.2014.00176

Abstract