To Treat Alzheimer’s and Other Disorders, a Detour Through the Nose

Groundbreaking research underway at Mass Eye and Ear is leading investigators toward a unique pathway for treating neurodegenerative disease: through the nose.

The studies, led by Benjamin Bleier, MD, Director of Endoscopic Skull Base Surgery, could help scientists bypass the most formidable obstacle to effective treatments for Alzheimer’s disease, Parkinson’s disease, and other conditions that add up to six percent of the global health burden.

That obstacle, the blood-brain barrier, is an anatomical paradox: the body’s way of protecting the brain from toxins in the environment. It also prevents 98 percent of therapeutics for brain-based conditions from reaching their target. Dr. Bleier realized that the technique used to reach the brain in endoscopic skull-base surgery—creating a hole between the nose and the brain, then reconstructing the area using nasal lining—could effectively be used as a method to deliver drugs directly to the brain. Nasal lining tissue is 1,000 times more permeable to drugs than the blood-brain barrier, and the parts of the brain involved in neurodegenerative disease are accessible directly beyond the opening surgeons typically create.

“When it comes to the nose, we like to say, ‘Location, location, location,’” noted Dr. Bleier. “The nasal cavity offers us incredible opportunities to study new drug delivery methods since it’s the only place where the central nervous system has direct access to the outside world.”

Several studies have emerged from the method, including mouse and rat models demonstrating the passage of large molecules a thousand times larger than typical drug molecules directly into the brain. One trial demonstrated that a neurotrophic factor, GDNF, preserved healthy brain cells in mice—effectively preventing the development of Parkinson’s disease. The trial garnered attention from media as well as the NIH, which just awarded Dr. Bleier’s team with a $2.5 million grant for further study.

“This is a platform technology that opens the door to delivery of effective treatments for a range of diseases—Alzheimer’s and Parkinson’s, and also pediatric seizure disorders and tumors,” said Dr. Bleier. “The horizon here is bright.”