Improving uptake over the blood-brain barrier
The blood-brain barrier (BBB) is limiting the efficacy of many potential therapies for neurological diseases. We are currently exploiting transferrin receptor (TfR)-mediated BBB-transfer and are generating novel TfR-targeting affibody molecules by selections against murine/human TfR from a phage-displayed affibody library.
After characterization of the binders in terms of affinity for TfR, cross-reactivity between human and murine TfR and biophysical properties, the anti-TFR affibodies will be fused to relevant affinity proteins. Improved BBB-transfer will be evaluated in preclinical studies using both ELISA on CSF samples as well as with PET imaging. We anticipate that the new TfR-specific affibodies will be of general value for many different kinds of drugs and diagnostic agents that benefit from increased uptake into CSF. Other advantages would be that many affibody-derived fusion proteins will likely be readily produced in E. coli.
Research funded by: The Schörling family foundation - Swedish FTD Initiative