Inhibition of formation of protease-resistant prion protein by Trypan Blue, Sirius Red and other Congo Red analogs.

Five compounds related to Congo Red were found to inhibit generation of protease-resistant prion protein in a cell-free system. In this assay Trypan Blue, Evans Blue, Sirius Red F3B, Primuline and Thioflavin-S were all more inhibitory than Congo Red itself. In scrapie-infected mouse neuroblastoma cells one compound, Sirius Red F3B, was capable of blocking the formation of protease-resistant prion protein to a similar extent as Congo Red; however, the other four compounds were less effective.

Inhibiting scrapie neuroinvasion by polyene antibiotic treatment of SCID mice.

The polyene antibiotic MS-8209 is currently one of the most effective drugs in the treatment of experimental scrapie. However, its mechanism of action and its site of intervention in the pathogenetical process of scrapie infection are largely unknown. It has been shown previously that the infection of immunodeficient SCID mice by the peripheral route provides a reliable model for direct scrapie neuroinvasion, bypassing the lymphoreticular system.

MS-8209, a water-soluble amphotericin B derivative, affects both scrapie agent replication and PrPres accumulation in Syrian hamster scrapie.

Amphotericin B (AmB) has been shown to delay hamster scrapie. Infectivity studies have been performed previously using AmB in order to understand the relationship between the accumulation of an abnormal isoform (PrPres) of the prion protein and 263K scrapie agent replication in the brain. The first study reported that AmB had no effect upon agent replication, although it delayed the development of both clinical signs and PrPres accumulation.

Effectiveness of polyene antibiotics in treatment of transmissible spongiform encephalopathy in transgenic mice expressing Syrian hamster PrP only in neurons.

To date very few drugs have favorably influenced the course of transmissible spongiform encephalopathies. In previous studies, the polyene antibiotics amphotericin B (AmB) and MS-8209 prolonged the incubation time in Syrian hamsters of the 263K strain of scrapie, but AmB had no effect against other scrapie strains in Syrian hamsters. In the present experiments using transgenic mice expressing Syrian hamster PrP in neurons only, MS-8209 extended the life spans of animals infected with the 263K strain but not the DY strain.