title: Dimethyl sulfoxide delays PrP sc accumulation and disease symptoms in prion-infected hamsters.
abstract: PrP(Sc), an aberrantly folded protein, is the only identified component of the prion, an agent causing fatal neurodegenerative diseases such as scrapie and bovine spongiform encephalopathy. Dimethyl sulfoxide (DMSO) has been shown to reduce the accumulation of PrP(Sc) in scrapie-infected (ScN2a) cells, and to inhibit its aggregation in vitro. In humans, DMSO was used successfully in the treatment of various peripheral amyloidotic diseases. Here we show that administration of DMSO to scrapie-infected hamsters significantly prolonged disease incubation time, as well as delayed the accumulation of PrP(Sc) in Syrian hamster brains. Interestingly, administration of DMSO to scrapie sick hamsters resulted in increased clearance of protease-resistant PrP in their urine. We conclude that although DMSO by itself may not be sufficient to cure prion diseases, it may be considered as a component in a 'cocktail' drug approach for these disorders. Also, urine PrP testing should be considered for the assessment of treatment efficacy.
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, 91120, Jerusalem, Israel.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Shaked
authors.forename: Roni
authors.initials: R
authors.lastname: Engelstein
authors.forename: Inbal
authors.initials: I
authors.lastname: Avraham
authors.forename: Esther
authors.initials: E
authors.lastname: Kahana
authors.forename: Ruth
authors.initials: R
authors.lastname: Gabizon
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D006224:Cricetinae; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008647:Mesocricetus; D018620:PrPSc Proteins / Q000378:metabolism* / Q000652:urine; D017096:Prion Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D012608:Scrapie / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects
chemical_list: D018620:PrPSc Proteins; D004121:Dimethyl Sulfoxide