Surgeons open a 'screen door' in the blood-brain barrier to successfully deliver drugs

Researchers have used a standard surgical technique in a brand new way to deliver drugs across the impenetrable blood-brain barrier. Because this barrier prevents approximately 98% of drugs from reaching the brain and central nervous system, the new development gives hope to many patients with difficult-to-treat neurological conditions.

In experiments in mice, researchers at Massachusetts Eye and Ear, Harvard Medical School, and Boston University in Boston, MA, replaced a section of the blood-brain barrier with nasal mucosa—which is more than 1,000 times more permeable—to create a “screen door” that allows drug delivery to the brain and central nervous system. They described their technique in an article online September 8, 2015 in Neurosurgery.

“We are developing a platform that may eventually be used to deliver a variety of drugs to the brain,” said senior author Benjamin S. Bleier, MD, Assistant Professor of Otology and Laryngology at Massachusetts Eye and Ear/Harvard Medical School.

He added, “Although we are currently looking at neurodegenerative disease, there is potential for the technology to be expanded to psychiatric diseases, chronic pain, seizure disorders, and many other conditions affecting the brain and nervous system down the road.”

ENT surgeons commonly use endoscopic approaches to remove brain tumors through the nose by making an opening through the blood-brain barrier to access the brain. Then they repair it with a nasal mucosal graft from adjacent nasal lining. The nasal lining protects the brain from infection just as the blood-brain barrier had done. Long-term clinical outcomes studies have established the safety and efficacy of these methods.

Dr. Bleier sought to test these techniques to deliver glial-derived neurotrophic factor (GDNF) for the treatment of Parkinson's disease in a mouse model. In this study, the researchers performed nasal mucosal graft and delivered GDNF in the mice, and then compared them with mice given direct intrastriatal injection of GDNF.

Behavioral assays and immunohistological analysis showed that the mucosal graft mice demonstrated the same results as the mice given direct injections.

The technique has the potential to benefit a large population of patients with neurodegenerative disorders, the investigators predicted.

“We see this expanding beyond Parkinson’s disease, as there are multiple diseases of the brain that do not have good therapeutic options,” Dr. Bleier said. “It is a platform that opens doors for new discovery and could enable drug development for an underserved population.”