ABSTRACT
Drug repositioning is a highly promising strategy for the discovery of new therapeutics and there is considerable interest in its application to Alzheimer's disease (AD), given the importance of AD and the continuing failure of conventional drug discovery programs. Common reasons for failures are that drugs fail to show a suitable safety profile and do not demonstrate slowing progression of AD, in some cases because they have low or no permeability through the blood–brain barrier (BBB). New strategies are therefore needed to generate efficient, safe, and economic drugs to treat AD, notably drug repositioning. Despite the considerable promise of the drug repositioning strategy, drug discovery for AD will remain a very challenging task, as shown by the recent failure of the monoamine oxidase B inhibitor sembragiline in a Phase II trial. It was hypothesized that sembragiline might delay progression of AD by reducing oxidative stress in the brain and lessening dopamine-related symptoms but no benefits were seen on cognition.
