Therapies for the Improvement of Stroke Recovery - Assessment of Clinical Trial Results

Recovery processes after stroke include restoration or compensation of function initially lost or newly acquired after injury. Therapeutic interventions can either directly improve these processes and/or inhibit processes that impede regeneration. Numerous experimental studies suggested a great opportunity for such treatments, but the results from recent large clinical trials with neuromodulators such as dopamine and fluoxetine have been rather disappointing. The reasons for this are manifold and involve the extrapolation of results from animal models to humans. Given the differences between animals and humans in genetic and epigenetic background, brain size and anatomy, cerebral vascular anatomy, immune system, as well as clinical function, and behavior, direct extrapolation is unlikely to work. Backward blockades include the incompatible adaption of clinical trial objectives and outcomes in clinical trials with regard to previous preclinical findings. For example, the clinical recovery trial design widely varies and has been characterized by the selection of different clinical endpoints, the inclusion a wide spectrum of stroke subtypes and clinical syndromes, and different time windows for treatment initiation after onset of infarction. This review will discuss these aspects based on the results of the recent stroke recovery trials with the aim to contributing to the development of a therapy that improves the functional outcome of a chronic stroke patient.