It is particularly important for the survival of striatal neurons that are affected prominently in HD and may protect against excitotoxicity.82 Several mechanisms have been implicated in the depletion of BDNF in HD, including transcriptional dysregulation83 and reduced axonal transport.84 Restoration of BDNF levels, or those of related neurotrophins such as glial cell–derived neurotrophic factor (GDNF), is of interest, but the challenges of delivering a protein-based therapeutic to the CNS are considerable. The gene discussed is GDNF; the disease is Huntington disease.