Huntington’s Disease (HD) is a devastating, mid-life onset neurodegenerative disorder with no treatment. We recently identified very high levels of the metabolite urea in the brains of HD patients. Over-production of urea is known to cause brain cell death and neurological symptoms in other contexts. Too much urea, or its highly toxic precursor ammonia, may therefore cause neurodegeneration in HD. Urea is produced by the liver, not the brain; raising the question: is the liver the biochemical origin of HD? This project aims to discover if urea and ammonia handling by the liver is defective in HD using our unique sheep model. Findings will support a significant paradigm-shift from HD as a brain disease to a whole-body disorder. Importantly, drugs already exist to treat high ammonia. We plan to test one of these drugs in the HD sheep model, raising the tantalising prospect of a readily available treatment for HD.