Can we re‐purpose drugs from the cardiology medicine cabinet? Should we look in the rheumatology, metabolic and hematology cabinets as well?

Abstract

AbstractBackgroundDespite substantial investment, the dementia drug development pipeline has failed to produce a convincing new pharmacological treatment. This situation is in stark contrast to drug development in oncology, metabolic and cardiovascular medicine, where many novel agents are entering phase III trials or clinical practice. Some of the commonly prescribed medications for brain disorders were originally developed for another therapeutic indication (memantine and tPA are examples). In this session we will consider whether re‐purposing existing or novel drugs from other disease areas could offer a treatment for dementia?MethodThe ultimate test of a new medication is the randomised controlled trial. Contemporary trials are costly. For drug repurposing we can exploit available data from trials and registries to inform the choice of candidate drugs and ‘de‐risk’ the development process. There are various approaches, and we will consider: expert consensus; systematic review and meta‐analysis; individual participant level evidence synthesis; genome wide association studies; drug wide association studies. Secondary analysis of existing trial and healthcare data can also inform the design, sample size and conduct of a repurposing study. As part of the Dementias Platform UK (DPUK) portfolio, we are utilising all these methods with the anticipation of selecting the most promising candidates to take forward to clinical trials.ResultThere are already good examples where existing data have informed or are informing drug repurposing studies. These include non‐steroidal and other anti‐inflammatory drugs (e.g. cilostazol); antithrombotic agents (e.g. dabigatran); antihypertensive or vasodilator medications (e.g. losartan, tadalafil); novel drugs developed for heart failure and diabetes mellitus (e.g. GLP1 agonists, such as liraglutide). Emerging data are already suggesting plausible candidates, while also giving new insights into the pathogenesis that underlies cognitive decline. We will share progress made within the DPUK Vascular group and offer a roadmap for future repurposing research.ConclusionThe search for an effective dementia intervention continues. It is possible that we already have useful medications that we can ‘borrow’ from other clinical fields. The increasing number of medications coupled with access to large volume, robust data‐sets creates an ideal landscape for selecting candidate drugs for repurposing.