Method of diagnosing and treating Huntington's disease

The present invention relates to the field of therapy for diseases of the central nervous system. In particular this invention concerns an “in vitro” method for early diagnosis of the onset of Huntington’s disease based on the assessment of abnormal adenylate cyclase activity and the binding to the adenosine A2A receptors and in the use of drugs that inhibit this activity for the prevention and/or treatment of this disease. This invention is based on the identification of an anomalous behaviour of the A2A adenosine receptor and its transduction system (adenylate cyclase enzyme) in cells genetically predisposed to develop Huntington’s disease and in circulating cells of affected patients as well as by overproduction of cyclic AMP following stimulation with A2A agonist compounds. This invention exploits this increase in the A2A receptors and overproduction of cyclic AMP as diagnostic markers in an vitro method for early detection of the onset of Huntington’s disease and to monitor its progression. The invention also described the use of compounds with A2A antagonist action that being capable of blocking this abnormal behaviour prevent pathological progression of the cell and thus form a class of drugs useful to the treatment and prevention of this disease. The present invention is based on studies performed by the applicants on an experimental genetic model of the disease and on platelets obtained from patients with Huntington’s disease. The experimental genetic model which reflects the genetic abnormality found in patients affected by Huntington’s disease is composed of neuronal cells, the genome of which contains the expansion of the CAG triplet. The cells thus modified express analogously to the in vivo pathological situation the mutant hungtintin protein. Working on this experimental model the applicants observed that the presence of mutant huntingtin in the neuronal cells affected by Huntington’s disease induces abnormal behaviour of the adenylate cyclase system responsabile for cyclic AMP synthesis and this behaviour is expressed as overproduction of cyclic AMP induced by stimulation with A2A agonist compounds. On the basis of these observations the present invention is aimed at a method for the diagnosis of Huntington’s disease that utilized as diagnostic marker an abnormal increase in the cellular production of cyclic AMP. In summary, the present invention comprises a method for the diagnosis of neurodegenerative diseases caused by genetic mutations due by increased repetitions of the CAG triplet. This method is characterised by using as a diagnostic markers either the increase in cellular production of cyclic AMP following to treatment with A2A agonists, or the increase of receptor density of A2A receptors. The present invention also comprises the use of A2A antagonist compounds for the treatment and/or prevention of genetic mutations characterised by increased repetitions of the CAG triplet.