Inherited neurodegenerative conditions such as Huntington's disease have proximal causes (a defective gene) and downstream causes (pathological events caused by that gene). Albert R. La Spada examines efforts to target bad genes with gene knockdown approaches on the eve of a clinical trial designed to silence the causative gene in familial amyotrophic lateral sclerosis. Masahisa Katsuno, Hiroaki Adachi and Gen Sobue examine the possibility of targeting a potentially damaging downstream event in Huntington's disease—dysregulated cholesterol metabolism in the brain.
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La Spada, A. Getting a handle on Huntington's disease: silencing neurodegeneration. Nat Med 15, 252–253 (2009). https://doi.org/10.1038/nm0309-252
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