Use of Neuropeptides for the prevention and treatment of alcoholism

Alcohol consumption is considered a major risk factor for disease and mortality worldwide according to the World Health Organization. Current therapies in alcohol use disorders (AUD) have limited efficacy, produce several adverse effects and present high rate of relapse. Therefore, there is a need of finding new biological targets to effectively modulate alcohol consumption. To this effect, there has been a lot of research to identify neurotransmitters that are implicated in AUD, such as GABA, glutamate, dopamine, noradrenaline, serotonin, and several other endogenous neuropeptides. Furthermore, most of the pharmaceutical gold standard treatments used nowadays against AUD aim at the receptors or the inhibitors of some of the aforementioned neurotransmitters, such as acamprosate or naltrexone. These treatments, however, do not show strong evidence in improving alcohol consumption outcomes for patients with AUD, the treatment's outcome is also very variable from patient to patient, and these drugs usually cause quite harsh side effects (such as anxiety, nausea or diarrhea). A Spanish university has developed and patented a method that describes the use of the Neuropeptide GAL (1-15) as a treatment for AUD. For the first time, it has been described how the Neuropeptide induces a strong reduction in ethanol consumption. This effect may be caused by the involvement of the Neuropeptide with the corpus striatum, which is a key region linked to the drug reward system. This mechanism involves changes in GAL receptors expression, it acts in the expression of immediately-early gene C-Fos and the gene related to the internalization of Rab5 receptors in the striatum; both enhance the neural activation and receptors in this area. The relevance of the corpus striatum as a target for the GAL(1-15) is supported by its ability to provoke the suppression of locomotor activity in rats after ethanol administration. This technology is currently at discovery stage. The effectiveness of the therapy has been proved with male Sprague-Dawley rats using intra-cerebroventricular microinjections of GAL and GAL(1-15) and the two-bottle choice test, in which it has been measured the voluntary ethanol consumption and preferences. Also, the corpus striatum was analyzed with RNA isolation and quantitative real-time PCR analysis. Furthermore, the pharmaceutical formulation that is being tested for the future use in humans is the inhalation of the peptide, as in this form, the neuropeptide can easily cross the blood-brain barrier. The research group that invented this technology is looking for partners interested in licensing the patent or in a technical cooperation.