Research Published December 19 2016
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Huntington’s disease, which affects about 6 000 individuals in France, is characterized by the progressive outbreak of motor, behavioral and cognitive disorders. Researchers from Alexis Brice’s team have participated in a collaborative project aiming to study the different versions of COMT gene also called COMT gene polymorphism. This gene is involved in dopamine degradation, which plays a major role in Huntington’s disease. The scientists showed differences in progression of motor and cognitive disorders based on the version of the gene carried by each patient. These results, published in PLOS One in September 2016, open the way to new therapeutic perspectives such as personalized treatments or COMT-specific treatments.

Huntington’s disease is a hereditary disease. It mainly affects the striatum, a cerebral structure involved in movements, before spreading to other regions of the brain. Symptoms are characterized by motor disorders, especially chorea, behavioral disorders, with anxiety, depression, aggressiveness, and cognitive disorders.

In this pathology, dopamine’s levels are decreased which has consequences on cognitive and motor functions. Scientists looked at the COMT gene which plays a role in dopamine degradation. Previous studies showed that COMT gene polymorphism, in other words the different versions of the gene that can be found in patients, is involved in the severity of cognitive and behavioral disorders in diseases like Parkinson’s disease or schizophrenia.

In order to study the impact of this polymorphism on the progression of cognitive, motor, behavioral and functional disorders in Huntington’s disease, researchers carried out a study following 438 patients with COMT gene mutations, between 1994 and 2011, at different stages of the disease. They also identified the version of COMT gene carried by each patient.

They showed that COMT gene polymorphism is involved in the progression of the disease and that it influences the evolution of the disease but not the age of onset. So, depending on the version of COMT gene carried by the patient, motor or cognitive decline is faster or slower.

These results open the way to new therapeutic avenues such as treatments adapted to the patient genetic mutation. An immediate application of these discoveries would be the use of COMT inhibitors or activators, already existing, as treatments. The results of this study are also useful for the setup of future clinical studies on Huntington’s disease.

Reference : COMT Val158Met Polymorphism Modulates Huntington’s disease Progression. Plos One, September 22, 2016.