J017 Testing metformin against cognitive decline in patients with Huntington disease

<h3></h3> Metformin is a widely prescribed drug to treat type 2 diabetes worldwide. This is a pleiotropic drug, that activates a range of targets, among which is AMP-activated protein kinase (AMPK). This enzyme is an activator of autophagy, which is one of the key pathways of misfolded protein clearance. From work done in the lab, in silico (analysis of Enroll-HD data) in vitro (Q111 cells) and in vivo (C. elegans and zQ175 mice), we concluded that metformin may be tested in patients of Huntington disease (HD), as a potential treatment to delay the appearance of phenotypes. Hence, here we present our ongoing clinical study, TEMET-HD (https://classic.clinicaltrials.gov/ct2/show/NCT04826692). It consists of a multicentric (nine spanish hospitals and the IIS La Fe (Valencia) as sponsor), double-blind, controlled with placebo essay to find out a positive tendency on cognitive performance of patients with HD, among other secondary targets. Once we open de study, if it confirms the expected tendency, we would like to amplify the number of patients, at the European level, and extend the period of treatment, in order to achieve reduction aggregation of mutant huntingtin, delay cognitive degeneration, and increase longevity of patients. In the future, we plan to test synergistic combinations of substances, that activate AMPK, to treat HD. We believe, that these objectives are highly compelling, and we are ardent supporters of this project. We believe it is crucial to extend its reach widely for the benefit of addressing this illness. Therefore, our poster presents a concise overview of the project, including: the study hypothesis, objectives, design, treatment, adverse effects, contraindications, and other pertinent information.