The results reported here demonstrate that experimentally induced decrease of the transcription elongation protein SUPT4H in brain and spinal cord tissues of murine models of Huntington’s disease results in selectively decreased expression of mutant huntingtin alleles, and that these events are associated with reduction of HTT protein aggregates, delay in the impairment of motor function seen in R6/2 HD mice as the animals age, and an increase in the R6/2 mouse lifespan. The gene discussed is SUPT4H1; the disease is Huntington disease.