Preclinical characterization of fingolimod as a potential therapeutic agent for stroke

Stroke is usually caused by the occlusion of a brain artery with a clot. It is the third most common cause of death and the most common cause of acquired physical disability in Ireland. The only available drug is only used in ~5% of patients (because most patients are either too far, or arrive too late to a specialized treatment center). Thus, it is crucial to find new treatments for stroke that would be effective in most patients. Fingolimod is used to treat multiple sclerosis. We and others have found that it is effective in rodent stroke models. These findings suggest that fingolimod is one of the most compelling stroke drug candidates ever characterized in animal studies. But hundreds of drugs effective in animals have failed to show efficacy in humans; this has tremendously raised the bar to justify the considerable expenses of a clinical trials.
We therefore propose to perform studies that are now considered essential before a potential stroke drug can move from animal to human testing. The idea behind this project is to better simulate the features of human stroke. For instance, while stroke is usually modelled in rodents by blocking blood supply to the brain with artificial filaments, we will mimic stroke with actual blood clots. We will also use older rodents, which have additional diseases often found in stroke patients (diabetes, high blood pressure, high cholesterol levels). Because stroke patients are treated with different drugs, we will study whether the presence of these drugs affects the efficacy of fingolimod, or increases the incidence of side-effects. If successful, our project should rapidly lead to clinical studies of fingolimod in stroke patients. Because these trials have a strong likelihood of success, these studies could lead to the first drug that would be effective in most patients.

Award Date

23 October 2015

Award Value

€329,949

Principal Investigator

Dr Christian Waeber

Host Institution

University College Cork

Scheme

Health Research Awards