title: Use of a 2-aminothiazole to Treat Chronic Wasting Disease in Transgenic Mice.
abstract: Treatment with the 2-aminothiazole IND24 extended the survival of mice infected with mouse-adapted scrapie but also resulted in the emergence of a drug-resistant prion strain. Here, we determined whether IND24 extended the survival of transgenic mice infected with prions that caused scrapie in sheep or prions that caused chronic wasting disease (CWD; hereafter "CWD prions") in deer, using 2 isolates for each disease. IND24 doubled the incubation times for mice infected with CWD prions but had no effect on the survival of those infected with scrapie prions. Biochemical, neuropathologic, and cell culture analyses were used to characterize prion strain properties following treatment, and results indicated that the CWD prions were not altered by IND24, regardless of survival extension. These results suggest that IND24 may be a viable candidate for treating CWD in infected captive cervid populations and raise questions about why some prion strains develop drug resistance whereas others do not.
authors.affiliation: Institute for Neurodegenerative Diseases.
authors.forename: David
authors.initials: D
authors.lastname: Berry
authors.affiliation: Institute for Neurodegenerative Diseases Department of Neurology, University of California San Francisco.
authors.forename: Kurt
authors.initials: K
authors.lastname: Giles
authors.affiliation: Department of Pathology.
authors.forename: Abby
authors.initials: A
authors.lastname: Oehler
authors.affiliation: Institute for Neurodegenerative Diseases.
authors.forename: Sumita
authors.initials: S
authors.lastname: Bhardwaj
authors.affiliation: Institute for Neurodegenerative Diseases Department of Pathology.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: DeArmond
authors.affiliation: Institute for Neurodegenerative Diseases Department of Neurology, University of California San Francisco.
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002460:Cell Line; D003670:Deer; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D053208:Kaplan-Meier Estimate; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000378:metabolism; D011817:Rabbits; D012608:Scrapie / Q000188:drug therapy / Q000401:mortality; D012756:Sheep; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D034081:Wasting Disease, Chronic / Q000188:drug therapy* / Q000401:mortality
chemical_list: D011328:Prions; D013844:Thiazoles; C004483:2-aminothiazole
keywords: chronic wasting disease; prion disease; survival extension; therapeutic; transgenic mice