Read with caution!
This post was written during early stages of trying to understand a complex scientific problem, and we didn't get everything right. The original author no longer endorses the content of this post. It is being left online for historical reasons, but read at your own risk.
Riemer 2008 has provided, to our knowledge, the only study so far looking at ibuprofen as a potential prion therapeutic. The mice suffered pretty severe adverse effects.
In choosing ibuprofen as a candidate compound, Riemer was presumably inspired by Lim 2001, who examined ibuprofen in a genetic Alzheimer’s mouse model and found that ibuprofen reduced the levels of the classic markers of Alzheimer’s pathology: IL-1β, GFAP, Aβ plaques. (Riemer cites Lim but does not actually discuss the reasons for the choice of ibuprofen). Lim in turn was inspired by evidence from Stewart 1997, a longitudinal observational study of ~1700 Americans which found a reduced relative risk of Alzheimer’s among people who took NSAIDs (such as ibuprofen) for at least than 2 years.
In prion disease, though, Riemer found it impossible to even tell if ibuprofen would have had an effect on the disease course, because the adverse effects were so pronounced:
Scrapie-infected ibuprofen-treated mice developed large erythema, followed by ulcerations of the outer genital region and massively enlarged urinary bladders (data not shown). About half of the ibuprofen-receiving mice had to be sacrificed due to their poor condition before they displayed typical symptoms of a late-stage scrapie infection. Uninfected ibuprofen-treated mice remained completely normal, indicating that the combination of drug treatment and ongoing prion disease development triggered these adverse responses.
Some amount of bladder enlargement is associated with scrapie infection in mice generally, and one study [Guenther 2001] also found a worsening of this effect with dapsone. But it sounds as though the adverse effect was much more pronounced with ibuprofen.