Crossing the blood-brain barrierSNI INSight May 2021
In the Nano Argovia project NANO-thru-BBB, an interdisciplinary team led by Professor Patrick Shahgaldian (FHNW) is developing a platform to design nanoparticles that can cross the blood-brain barrier (BBB). The project involves researchers from the School of Life Sciences (FHNW), the University of Basel and the industrial partner Perseo Pharma AG (Muttenz).
The blood-brain barrier is a complex, selective barrier that protects the brain from harmful substances or pathogens found in the bloodstream. Nutrients needed by the brain enter the brain only through specific, controlled transport processes, while numerous macromolecules are denied entry. Biological therapeutics that could be used to treat neurological diseases in the brain are also generally unable to cross the blood-brain barrier.
However, nanoparticles in which these biological macromolecules are “packaged” can pass the barrier under certain circumstances. To date, however, no study exists that systematically identifies which surface properties the optimal nanotransporters should have.
The research groups of Professor Patrick Shahgaldian, Professor Laura Suter-Dick (both FHNW), Professor Jörg Huwyler (University of Basel) and Dr. Yves Dudal and Dr. Emilie Laprévotte (both Perseo pharma) are now planning to develop a new technological platform that will enable an optimized design of such nanoparticles.
Based on a novel method of combinatorial surface modification, the researchers will study the chemical structure and nanoparticle design and test them on cellular BBB models (in vitro) and on zebrafish models (in vivo). Supported by computer analyses, the scientists will be able to determine the most appropriate nanoparticle structure that enables passage through the blood-brain barrier.
Specifically, the project aims to introduce enzymes into the brain through the blood-brain barrier that can be used to treat hereditary lysosomal storage diseases. In the long term, the project will provide a solid database to conduct clinical trials with nano-formulated enzymes against these metabolic diseases.
“Approximately thirty enzyme replacement therapies are available on the market for the lifelong treatment of a family of inherited metabolic disorders called lysosomal storage diseases. However, these drugs do not reach the patient’s brain. Consequently, the children can experience life but most often grow with very significant mental issues. The possibility to bring these therapeutic enzymes to the brain would represent a major breakthrough for all these patients. Perseo pharma is highly motivated to provide a preclinical proof of concept for this breakthrough and to further develop a new generation of enzyme replacement therapies.”
Dr.-Ing. Yves Dudal, CEO of Perseo pharma