Methods and compositions for treating Huntington's disease

A method of increasing levels of at least two of PDE10a, DARPP-32, DRD1 and DRD2 in a medium spiny neuron (MSN) of a mouse or human subject, the method comprising administering to the striatum of the subject a genetic repressor comprising a polynucleotide encoding a zinc finger protein DNA-binding protein (ZFP) comprising 3 to 6 zinc finger domains comprising the recognition helix regions in the order shown in a single row of Table 1B, which ZFP binds to a target sequence as shown in Table 2B, wherein the repressor represses transcription of a mutant Huntingtin (Htt) gene, thereby increasing levels of at least two of PDE10a, DARPP-32, DRD1 and DRD2 in the subject at least 30% as compared to a control subject which was not administered the genetic repressor.