Patients with diseases that affect the central nervous system (CNS), such as Parkinson’s disease, may one day better benefit from therapeutics developed to target them via a novel delivery system that more effectively and safely bypasses the blood brain barrier to deliver the needed dose of therapy, according to new research published in Neurosurgery.
“Current methods to bypass the blood brain barrier have a significant amount of problems associated with them, the largest being they require the penetration of the brain and the implantation of foreign bodies,” said Benjamin S. Bleier, MD, assistant professor in the department of otology and laryngology at Harvard Medical School and Massachusetts Eye and Ear Infirmary in Boston and lead author of the study.
Up to 98% of potential neurpharmaceuticals cannot reach the CNS due to the blood brain barrier. Current techniques to bypass the blood brain barrier are associated with significant morbidity and complication rates of up to 40%.
In a proof of principle study, Dr. Bleier and his colleagues tested a novel delivery system in a mouse model in which they created a semipermeable window in the blood-brain barrier using autologous tissues to allow high molecular weight drug delivery to the CNS. This was achieved using an established surgical method to reconstruct defects of the skull base following endoscopic skull base surgery that involves engrafting semipermeable nasal mucosa within a surgical defect in the blood brain barrier. Using this method, the investigators were able to use the mucosal graft to create a conduit to the CNS though which drugs can be delivered.
“The mucosal graft is about 1,000 times more permeable than the native blood brain barrier,” said Dr. Bleier, which he added theoretically enables the delivery of the entire molecular weight therapeutics into the CNS through the nose.
The researchers found that molecules up to 500 kDa could be transported directly to the brain through the mucosal grafts, and that this method could be used to deliver glial-derived neurotrophic factor to prevent the development of Parkinson’s disease in a mouse model.
Dr. Bleier said this study showed a way to deliver drugs to the brain transmucosally, but now the challenge is to find a way to control that delivery. To that end, he said the next logical step is to develop drug-eluting polymers that can be implanted over the graft, which can be tuned and highly controlled to deliver a specific drug at a specific dose over a specific time.