Table 2.
PrP lowering is effective across prion strains
| ASO treatment experiment | genetic experiment | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| saline | active ASO 1 | Δ | wild-type | Prnp+/− | Δ | |||||
| strain | days | N | days | N | days | N | days | N | ||
| RML | 153±4 | 7 | 211±3 | 8 | +38% | 150±5 | 4 | 427±7 | 6 | +184% |
| 22L | 171±6 | 8 | 250±11 | 8 | +46%* | 160±6 | 6 | 275±7 | 6 | +71% |
| Fukuoka-1 | 159±4 | 7 | 217±7 | 7 | +37% | 158±9 | 6 | 248±34 | 6 | +57% |
| ME7 | 160±14 | 6 | 199±10 | 6 | +24% | 146±11 | 7 | 289±23 | 5 | +99% |
| OSU | 152±6 | 8 | 206±9 | 7 | +36% | 152±3 | 6 | 338±65 | 5 | +122% |
| RML[ASO] | 158±3 | 6 | 273±16 | 5 | +73% | |||||
Days (mean±sd) to symptomatic endpoint for animals that received two 500 μg doses of ASO versus saline, at −14 and at 76 dpi (left, details in Supplementary Figure S1), or for untreated Prnp+/− versus wild-type animals (right, details in Supplementary Figure S2). For overall survival curves see Supplementary Figures S1 and S2. Following established nomenclature (30), RML[ASO] denotes prions from the brains of mice infected with RML prions and treated with ASOs (see Methods). Studies conducted at the Broad Institute. *Results from repeat experiment, see Supplementary Figure S1 for details.