Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male Survival in Models of Prion Disease.
Level 5 - mechanism / opinion, no new human data
Bench, cell culture, and animal models without human clinical data
PubMed 25972546 · doi:10.1128/JVI.01165-15
What was done
The authors evaluated the therapeutic efficacy of the bile acids tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) in preclinical models of prion disease. Testing was conducted using cell-free aggregation assays, acutely and chronically infected cell cultures, prion-infected cerebellar slice cultures to assess neuronal loss, and RML prion-infected mice treated with UDCA to assess survival, astrocytosis, phosphorylated eIF2 levels, and postsynaptic density protein 95.
What was found
The abstract reports no numerical values or statistics. Reported qualitative findings include: - TUDCA and UDCA reduced PrP conversion in cell-free assays and infected cell cultures by decreasing PrPSc seeding ability. - Both compounds reduced neuronal loss in prion-infected cerebellar slice cultures. - UDCA reduced astrocytosis and prolonged survival in RML prion-infected mice, with effects limited to male mice. - Phosphorylated eIF2 levels were increased at early time points, which correlated with reductions in postsynaptic density protein 95.
Why it matters
Prion diseases lack disease-modifying therapies. Because UDCA and TUDCA are already FDA-approved, orally bioavailable, and brain-penetrant, demonstrating dual anti-conversion and neuroprotective mechanisms in models suggests potential for translational exploration.
Limits
The study is entirely preclinical (in vitro, ex vivo slice culture, and animal models) with unstated sample sizes (n is unknown from the abstract). The survival benefit in vivo was restricted to male mice, indicating unexplained sex-specific metabolism or response differences, and efficacy in human prion diseases remains unstudied.
Cited by
- supports TUDCA crosses the blood-brain barrier.