Before drugs designed for prion protein existed, researchers tested medicines already approved for other uses. The completed studies covered flupirtine (Germany, 28 people), pentosan polysulfate (UK, 7, and Japan, 11), quinacrine (France, 32; UK, 107; US, 54) and doxycycline (France and Italy, 121). Only people with symptoms took part, most with sporadic CJD. The doxycycline trial was randomised and placebo controlled, and its result was negative for survival. It ran in France and Italy.
Two UK studies, one of quinacrine and one of pentosan polysulfate, appeared to show benefit, but the source attributes those results to confounding, and the randomised US quinacrine trial found none. Lessons recorded from this period include stronger laboratory evidence before a trial, earlier diagnosis, trials in people with a disease-causing PRNP variant who have no symptoms, and use of the MRC scale as an outcome. The trials also showed that multinational studies can run in a rare, fast disease. Current approaches are listed under therapies.