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• W2803103630 abstract "ABSTRACT Prion diseases are a group of neurodegenerative diseases associated with the misfolding of the cellular prion protein (PrP C ) into the infectious form (PrP Sc ). There are currently no treatments for prion disease. Bile acids have the ability to protect hepatocytes from apoptosis and are neuroprotective in animal models of other protein-folding neurodegenerative diseases, including Huntington's, Parkinson's, and Alzheimer's disease. Importantly, bile acids are approved for clinical use in patients with cirrhosis and have recently been shown to be safe and possibly effective in pilot trials of patients with amyotrophic lateral sclerosis (ALS). We previously reported that the bile acid ursodeoxycholic acid (UDCA), given early in disease, prolonged incubation periods in male RML-infected mice. Here, we expand on this result to include tauro-ursodeoxycholic acid (TUDCA) treatment trials and delayed UDCA treatment. We demonstrate that despite a high dose of TUDCA given early in disease, there was no significant difference in incubation periods between treated and untreated cohorts, regardless of sex. In addition, delayed treatment with a high dose of UDCA resulted in a significant shortening of the average survival time for both male and female mice compared to their sex-matched controls, with evidence of increased BiP, a marker of apoptosis, in treated female mice. Our findings suggest that treatment with high-dose TUDCA provides no therapeutic benefit and that delayed treatment with high-dose UDCA is ineffective and could worsen outcomes." @default.
• W2803103630 created "2018-06-01" @default.
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• W2803103630 date "2018-08-01" @default.
• W2803103630 modified "2023-09-26" @default.
• W2803103630 title "High Dose and Delayed Treatment with Bile Acids Ineffective in RML Prion-Infected Mice" @default.
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• W2803103630 doi "https://doi.org/10.1128/aac.00222-18" @default.
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