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Huntington’s disease (HD) is a devastating autosomal dominantly inherited neurodegenerative disease for which there is currently no effective disease modifying therapy. The genetic predictability of HD provides an opportunity for early therapeutic intervention many years before overt symptom onset and at a time when reversal or prevention of neural dysfunction may still be possible. As HD is monogenetic, fully penetrant, and characterised by a long premanifest phase, it is emerging as a potential model for studying therapeutic intervention in other neurodegenerative conditions such as Alzheimer’s or Parkinson’s disease where no preclinical diagnostic tests exist. Understanding of HD pathogenesis is evolving, and there are a number of candidate therapeutics with potential disease-modifying effects that are currently being tested. In my talk, I will update on insights into HD pathogenesis, new data to understand the neurobiology of the preclinical phase of neurodegeneration and neural compensation and plasticity in HD, and give an overview on exciting advances working towards HD gene silencing in humans.
