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Using GABAA receptor modulators to alleviate neuropsychiatric symptoms in Huntington's disease.

Huntington’s disease (HD) is a devastating, inherited neurodegenerative disorder, characterised by the cognitive, motor and neuropsychiatric symptoms. The neuropsychiatric symptoms emerge early in the course of the disease, are a key cause of disability and include apathy, irritability, impulsivity, anxiety and depression. No therapeutic interventions exist to alleviate these symptoms; instead, standard psychiatric drugs are used with limited success. Based on the distribution of specific GABAA subunits in brain regions relevant to HD, we hypothesise that novel drugs targeting these subunits should alleviate key neuropsychiatric features of HD. Importantly, they should achieve this without the debilitating side effects (eg sedation and hypnotic effects) associated with existing drugs targeting GABAA. We will test these drugs in two rodent models of HD using sensitive behavioural tests and biochemical analysis of brain tissues. This work has the potential to revolutionise the treatment of these psychiatric symptoms.

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