Researchers discover early identifiers of Huntington's disease

Researchers from the University of Surrey and University of Cambridge have discovered early warning signs of Huntington’s disease in a new study.

Scientists uncovered early biomarkers of the disease during examinations of sheep carrying the human HD mutation.

Huntington’s disease is a genetic neurodegenerative disorder caused by the expansion of a CAG repeat in the HD gene. It affects over 6,700 people in the UK and is incurable. The sheep model of Huntington’s disease has been developed to increase knowledge about Huntington’s disease.

The study identified clear metabolic changes in the affected animals, which up until this point, had displayed no signs of the illness. The findings reveal that Huntington’s disease affects important metabolic processes in the body prior to the appearance of physical symptoms.

The researchers took blood samples from normal and HD animals every two hours over a 24-hour period to assess their metabolic profiles. The sheep in the study were monitored in a well-controlled setting, removing any outside influences of which previous studies had been affected by.

Blood measurements showed differences in the biochemistry of the sheep carrying the HD gene, compared to the normal sheep.

Changes were observed in 89 of the 130 metabolites measured in their blood including increased levels of amino acids, arginine and citrulline, and decreases in sphingolipids and fatty acids that are commonly found in brain and nervous tissue.

The alterations suggest that the urea cycle and nitric oxide pathways, two vital body processes, are dysregulated in the early stages on Huntington’s disease and that the illness affects the body long before physical symptoms appear.

The researchers believe that the identification of the biomarkers can help to track disease in pre-symptomatic patients, and they could also help researchers develop strategies to remedy biochemical abnormalities.

Professor Debra Skene from the University of Surrey said: “Metabolic profiling has revealed novel biomarkers that will be useful to monitor Huntington’s disease progression. Our research shows that this disease affects the body in a number of ways before the tell-tale signs of Huntington’s disease become visible. This is not the end of our research, we will continue to observe these sheep and study how this disease evolves.”

Professor Jenny Morton from the University of Cambridge said: “Despite its devastating impacts on patients and their families, there are currently limited treatments options, and no cure for Huntington’s disease. The development of objective and reliable biomarkers that can be rapidly measured from blood samples becomes immeasurably important once clinical trials for therapies begin. The more we learn about this devastating illness the better chance we have of finding a cure.”