Alzheimer's disease - R-flurbiprofen
Non-steroidal anti-inflammatory drugs have been shown to have an effect in preventing both Alzheimer\'s disease and cancer in the large epidemiological studies carried out since their use became widespread. However, because of their dose-limiting effects on the gastrointestinal tract, they are not suitable for general prophylactic use.
Non-steroidal anti-inflammatory drugs have been shown to have an effect in preventing both Alzheimer's disease and cancer in the large epidemiological studies carried out since their use became widespread. However, because of their dose-limiting effects on the gastrointestinal tract, they are not suitable for general prophylactic use.
These side-effects result from the drugs' inhibition of cyclooxygenases 1 and 2. They are generally given as racemic mixtures, and it appears that the COX activity results from one enantiomer. Rather than being inactive, it now appears that the other enantiomer may have other biological effects. These include the R-enantiomer of the NSAID flurbiprofen, which has shown antiabyloidogenic activity, and also acts as a nuclear factor NF-B modulator.1 Its potential in preventing and treating Alzheimer's disease, and also for the treatment of prostate cancer, is being investigated by Myriad Genetics, having initially been developed by Encore Pharmaceuticals and Loma Linda University in the US.
In a randomised, double blind, placebo-controlled trial, 207 patients with a mean age of 75 and suffering from mild to moderate Alzheimer's disease were given 400 or 800mg of the drug or placebo twice a day for a year.2 In those given the higher dose, there was a 34% reduction in the rate of cognitive decline compared with those given placebo. More than four-fifths of the subjects continued into a year-long extension to the study, with those in the placebo group being randomised to receive one of the two doses of the drug. The rate of decline in cognition slowed compared with the first year of the trial.
An open label multiple dose Phase IIa trial in 23 patients with late stage prostate cancer has also been carried out.3 More than half of the subjects had hormone refractory forms of the disease. They were all given 200 to 1200mg of the drug orally once a day, or 800mg twice a day for eight to 16 weeks. Fifteen of these subjects continued into an extended dosing phase for a further period of eight to 16 weeks. Twelve of the 23 subjects showed a reduction in prostate-specific antigen velocity and an increase in PSA doubling time during treatment. Treatment was well tolerated.