Table 2. ISRIB treatment prevents clinical signs of prion disease in infected mice.
Vehicle-treated mice | ISRIB-treated mice | |
---|---|---|
n=9 | n=12 | |
Early indicator signs | ||
Rigid tail | 9/9 | 7/12 |
Hind limb clasping | 8/9 | 7/12 |
Unsustained hunched posture | 4/9 | 0/12 |
Mild loss of coordination | 9/9 | 7/12 |
Confirmatory signs | ||
Impairment of righting reflex | 5/9 | 0/12 |
Dragging of limbs (front/hind) | 2/9 | 0/12 |
Sustained hunched posture | 3/9 | 0/12 |
Scrapie incubation | ||
Number of animals succumbing to prion disease | 9/9 | 0/12 |
Prion disease is diagnosed by the presence of two confirmatory clinical signs or two early indicator and one confirmatory clinical signs. Nine out of nine vehicle-treated mice exhibited a mixture of early indicator and confirmatory clinical signs, indicating the development of clinical prion disease. Seven out of 12 ISRIB-treated mice exhibited early indicator clinical signs, but none progressed to confirmatory signs and were not clinical diseased, demonstrating the protective effects of ISRIB treatment on prion disease progression (vehicle treated n=9, ISRIB treated n=12)