Researchers use nasal lining to breach blood-brain barrier

Neurodegenerative and central nervous system (CNS) diseases represent a major public health issue affecting at least 20 million children and adults in the United States alone. Multiple drugs exist to treat and potentially cure these debilitating diseases, but 98 percent of all potential pharmaceutical agents are prevented from reaching the CNS directly due to the blood-brain barrier.

Using mucosa, or the lining of the nose, researchers in the department of Otology and Laryngology at the Massachusetts Eye and Ear/Harvard Medical School and the Biomedical Engineering Department of Boston University have demonstrated what may be the first known method to permanently bypass the , thus opening the door to new treatment options for those with neurodegenerative and CNS disease. Their study is published on PLOS ONE.

Many attempts have been made to deliver drugs across the blood-brain barrier using methods such as osmotic disruption and implantation of catheters into the brain, however these methods are temporary and prone to infection and dislodgement.

"As an endoscopic surgeon, I and many other researchers have helped to develop methods to reconstruct large defects between the nose and brain using the patient's own mucosa or nasal lining," said Benjamin S. Bleier, M.D., at Mass. Eye and Ear and HMS Assistant Professor.

Study co-author Xue Han, Ph.D., an assistant professor of Biomedical Engineering at Boston University, said, "The development of this model enables us to perform critical preclinical testing of novel therapies for neurological and psychiatric diseases."

Inspired by recent advances in human endoscopic transnasal skull based surgical techniques, the investigators went to work to develop an of this technique and use it to evaluate transmucosal permeability for the purpose of direct drug delivery to the brain.

In this study using a mouse model, researchers describe a novel method of creating a semi-permeable window in the blood-brain barrier using purely autologous tissues to allow for higher molecular weight drug delivery to the CNS. They demonstrated for the first time that these membranes are capable of delivering molecules to the brain which are up to 1,000-times larger than those excluded by the blood-brain barrier.

"Since this is a proven surgical technique which is known to be safe and well tolerated, this data suggests that these membranes may represent the first known method to permanently bypass the blood-brain barrier using the patient's own tissue," Dr. Bleier said. "This method may open the door for the development of a variety of new therapies for neurodegenerative and CNS disease.

Future studies will be directed towards developing clinical trials to test this method in patients who have already undergone these endoscopic surgeries."

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JVK
1 / 5 (1) Apr 25, 2013
This 'novel' therapeutic treatment approach [e.g., for Alzheimer's] also avoids the problematic and invasive neural stem cell replacement, and the treatment appears to follow from a presentation I made in 1992: Luteinizing hormone: The link between sex and the sense of smell? Annual Meeting of the Society for the Scientific Study of Sex. San Diego, California. Nov 12-15. It is great to see others begin to realize the importance of how olfactory/pheromonal input crosses the blood/brain barrier in brain dysfunction, nonetheless. Can you imagine how much progress might otherwise have been made if cause and effect had been established more than two decades ago? See, for example: "Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis" http://www.freshp...8009.php