BDNF and Huntington disease: PDE10A regulates cAMP and cyclic guanosine monophosphate signalling, synaptic plasticity and the response to cortical stimulation.66,67 PDE10A inhibition or genetic deletion produces numerous CRE–related gene expression changes68 and alterations in synaptic function69 suggested to be beneficial in schizophrenia and HD.67 In the R6/2 mouse, PDE10A inhibition with TP-10 ameliorated motor deficits, reduced striatal atrophy and increased brain-derived neurotrophic factor (BDNF) levels.70 Detailed study of PDE10A and its pharmacological inhibition is underway to validate it as a target in HD.