Novel recovery treatment for Stroke: enhanced brain delivery of Cyclosporin A

Purpose and goal

Based on NeuroVive´s and toBBB´s technology platforms, the objectives with the project were to combine these two technologies to develop formulations for optimal delivery of NeuroSTAT (cyclosporin A) in combination with the G-technology, over the blood brain barrier to the brain in patients suffering from stroke. The new chemical entity would have the potential to reduce the ischemic area after an stroke incident and thereby improving the clinical outcome in these patients. Cyclosporin A, acting as a cyclophilin inhibitor at the mitochondria level, is strongly neuroprotective.

Results and expected effects

It was expected that the G-Technology would improve delivery of cyclosporin A (NeuroSTAT) over the blood barin barrier and thereby increase the concentration of the drug in the brain. The result would be a more effective inhibition of cyclophilin D and prevention of further cell and tissue damage following a stroke and the ischemic event. A number of different formulation was tried in cell and animal stroke models but it was not possible to obtain a significant effect on cell death and tissue damage of the combined technologies and various lipid formulations.

Approach and implementation

Technologies justifying drug development for treatment of stroke; (i) Cyclosporin A (NeuroSTAT) is strongly neuroprotective, and (ii) the G-Technology enables transport of drugs over the blod-brain barrier to the brain. The two technologies were combined and a number of different lipid formulations were developed. The formulations were tested in various cell and animal stroke models. Analysis of the projects demonstrated limited effects of the formulations with CsA on damaged brain tissue in induced stroke models. These effects did not justify further preclinical studies.