Fig. 1.

Relationship of IND24 dosing schedule to prion strains and survival. (A) Efficacy of IND24 in cell culture. CAD5 cells infected with RML, ME7, or 22L prions, as indicated, were treated with IND24 at 2 or 10 µM for 5 days, and levels of PK-resistant PrP were determined by immunoblot. PrP was detected using the chimeric Fab D13. RML-infected cells were at passage 14, and ME7- and 22L-infected cells were at passage 10. Molecular weight markers of migrated protein standards represent 20 and 30 kDa. (B) Efficacy of IND24, expressed as the survival index, for mice expressing wild-type levels of PrP inoculated with RML (circles), ME7 (triangles), or 22L (squares) prion strains. IND24 intervention at 210 mg/kg per day was initiated at different time points, which are shown as the relative percentage of the incubation period for each prion strain. Error bars represent S.E.M. (C) Mean incubation periods in wt mice inoculated with RML prions with different IND24 dosing regimens. IND24 dosing shown in gray; no treatment indicated in white. Intermittent dosing is more effective than continuous dosing initiated at 1 dpi; however, continuous dosing prophylactically produces a dramatic increase in survival extension. Error bars represent S.E.M. (D) Efficacy expressed as in (B) but in Tg4053 mice overexpressing PrP inoculated with the RML prion strain.