Project Details
Projekt
Standardization of animal models and outcome parameters
Applicants
Dr. Friederike Langhauser; Dr. Gemma Llovera
Subject Area
Molecular and Cellular Neurology and Neuropathology
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 405358801
Thrombolysis with tissue plasminogen activator (tPA) and mechanical thrombectomy are the only clinically approved treatment options for ischemic stroke. Just a minority of patients are eligible to receive these specific treatment options due to the narrow therapeutic time window and multiple exclusion criteria. Although numerous experimental therapies have shown promising results in animal models of stroke, none of them has yet been translated into clinical use for stroke patients. Reasons include poorly designed preclinical and clinical studies, biased selection of substances, and underpowered trials with overly ambitious and physiologically irrelevant therapeutic time windows. To overcome this “reproducibility crisis” a preclinical randomized controlled trial (pRCT), together with operational and statistical guidelines, is an important tool to improve preclinical research. During the first funding period, standard operating procedures (SOPs) were defined and trained within the Research Unit and the infrastructure for conducting a preclinical multicenter RCT was prepared. In our collaborative project, we now want to perform two independent fully powered pRCTs to test the efficacy of two therapeutic candidates on post-stroke recovery. To this end, we will evaluate whether two different treatments (P2X7-targeting nanobodies & Plasmakallikrein antibodies) can protect against brain injury in the chronic phase of ischemic stroke in two different experimental stroke models, permanent and transient middle cerebral artery occlusion models. To account for possible gender differences in treatment efficacy, both male and female mice will be included in the pRCTs.In addition, we will continue to train new collaborators in the protocols defined in the first funding period and support all members of the consortium to ensure complete homogeneity within our research unit.By conducting these pRCTs with a high degree of harmonization within our consortium, we aim to improve the quality of preclinical research and will provide an intermediate step between exploratory preclinical studies and clinical efficacy trials.
DFG Programme
Research Units
