This conclusion is also supported by loss-of-function PRNP alleles observed in healthy human subjects16; (iii) strong experimental evidence demonstrates that lowering the expression of PrP would confer therapeutic benefits in prion diseases, and possibly other neurodegenerative disorders linked to the toxicity-transducing activity of the protein15,22; (iv) however, multiple previous failures to target the native conformation of PrP pharmacologically suggest that this protein could be an undruggable factor23,24. The gene discussed is PRNP; the disease is prion disease.