THE PERIPHERAL A2A RECEPTOR AS A BIOMARKER IN HUNTINGTON DISEASE

Huntington's disease (HD) is a genetic, neurodegenerative, motor disease caused by an expansion of a CAG triplet repeat in the gene encoding for Huntingtin (htt). Degeneration mainly involves a specific neuronal population in basal ganglia, a cerebral area involved in regulation of motor activity. Among the various neurotransmitter systems that have been implicated in HD development, the adenosine system seems to play an important role through the activation of the A2A adenosine receptor subtype located on these neurons. Recent studies performed on neural cells engeneered to express human mutant htt have highlighted the presence of an aberrant amplification of the signalling of the A2A adenosine receptor, suggesting a role in the development of the pathology. A main aim of the present project is to verify if this aberrant receptor behaviour is also expressed in circulating blood cells (platelets, lymphocytes and neutrophils) of HD patients, and could be exploited as a biomarker of the disease, to establish its exact onset and to evaluate the efficacy of potential therapeutic interventions with time, with an higher accuracy with respect to the genetic test. Such a test would be based on the measurement of a receptor parameter on blood cells obtained from patients, and would hence be fully justifiable also from an ethical point of view. The project will include the analysis of specific A2A receptor parameters in patients with HD at different stages (in comparison with healthy subjects), as well as in asymptomatic mutation carriers. The latter approach will enable us to verify if the receptor aberration is already present before the onset of clinical symptoms and could therefore be exploited to anticipate its development.