Aerosol travels nerve from nose to brain to treat stroke in mice

SAN ANTONIO (Dec. 17, 2008) — UT Health Science Center San Antonio researchers, working in a mouse model of stroke, are delivering neuroprotective drugs to the brain by spraying them onto the lining of a nerve in the nose. The goal is to prevent the death of brain cells after stroke.

The drugs are delivered via the olfactory nerve, which controls the sense of smell. In humans, connections from this nerve extend to areas controlling speech, comprehension and opposite-side movement, all of which may be damaged by an ischemic stroke resulting in devastating disabilities. Ischemia is a lack of oxygen resulting from clots blocking blood vessels.

“This nerve is a highway to the brain through which we can easily deliver brain tissue-preserving agents, and we think this method of delivery may be good for eight to nine hours after a stroke begins,” said David F. Jimenez, M.D., professor and chairman of the Department of Neurosurgery at the Health Science Center.

Stroke, the nation’s third-leading killer, can strike anyone at any time. As the minutes pass, brain tissues die from lack of oxygen. Tissue plasminogen activator (tPA), a clot-busting drug, is generally very effective if administered within the first three hours of stroke onset.

After three hours, surgery is often necessary to bust the clot or retrieve it. After six hours, it is difficult to limit stroke damage by any means. If aerosol drug delivery through the olfactory nerve can be moved from the mouse model to human clinical trials and eventually to federal approval, it would potentially expand that window.

Preliminary studies in the mouse model are extremely promising.

“This method offers direct access to the brain via topical application through the nose,” said Murat Digicaylioglu, M.D., Ph.D., assistant professor and director of neurosurgical research in the Department of Neurosurgery. “In mice it travels from the nose to crucial brain regions within 20 minutes. It is not affected by the blood-brain barrier, which prevents many drugs that are administered by injection from entering the brain.”

In treated mice, the volume of brain tissue killed by stroke is two-thirds less than that of untreated mice, Dr. Digicaylioglu said.

“Most importantly, we have seen significant improvement in neurological outcome after stroke with this treatment, including motor function and behavioral measures such as ability to navigate a maze,” he said.

If a clinical trial is conducted in the future and the delivery system is approved for use in humans, it is plausible to assume it could be carried aboard ambulances as a frontline therapy for immediate care of stroke patients. “This is a very exciting possibility,” Dr. Jimenez said.

One day, if proven, the delivery system even could be used to administer therapies for Alzheimer’s disease, Parkinson’s disease and other neurodegenerative diseases, he said.

The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $668 million, the Health Science Center is the chief catalyst for the $15.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 23,000 graduates (physicians, dentists, nurses, scientists and other health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, dentistry and many other fields. For more information, visit www.uthscsa.edu.



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