University of South Florida researchers report that a novel needle-free vaccine approach is effective and safe in clearing brain-damaging plaques from a mouse model of Alzheimer's disease. The transdermal, or across the skin, vaccination, may offer a simpler way of preventing or treating the devastating neurodegenerative disease with less likelihood of adverse immune reactions.
The study was published online this week in The Proceedings of the National Academy of Sciences.
"While many groups have shown vaccinating against the beta amyloid protein (Ab) can reduce Alzheimer's-like pathology including certain cognitive deficits, this study is the first to demonstrate that immunization using the skin may be an effective way to reduce Ab pathology," said senior study author Jun Tan, PhD, MD, director of the Neuroimmunology Laboratory at the Institute for Research in Psychiatry, USF Department of Psychiatry.
"The beauty is that something as simple and non-invasive as a skin patch could potentially be a promising therapy for Alzheimer's disease," said study coauthor Terrence Town, PhD.
The Alzheimer's vaccine works by triggering the immune system to recognize Ab -- a protein that abnormally builds up in the brains of Alzheimer's patients -- as a foreign invader and attack it.
Previous research on an injectable Alzheimer's vaccine proven safe and effective in an animal model was suspended indefinitely when the initial clinical trial caused brain inflammation and death in a small percentage of patients. These serious side effects were secondary to an autoimmune reaction, which occurred when immune cells aggressively attacked the body's own proteins produced by the vaccine.
The USF researchers targeted the skin as the route of vaccine delivery in mice bred to develop age-related brain degeneration mimicking Alzheimer's. They found that transdermal immunization with Ab does not appear to trigger specific toxicities associated with past immunization strategies.
Specialized immune cells prevalent in the skin, called Langerhans, may direct the body's reaction to the vaccine toward a response that is beneficial instead of overly aggressive and ultimately harmful, Dr. Tan said.
The USF researchers plan to further test whether the transdermal vaccine can curb memory loss in Alzheimer's mice as well as reduce their "senile" plaque burden. "If those studies show clear cognitive benefits," Dr. Tan said, "we believe clinical trials to evaluate a beta amyloid skin patch or topical cream in patients with Alzheimer's would be warranted."
William Nikolic, a PhD candidate of the USF Department of Molecular Medicine, and Yun Bai, PhD,MD, were co-first authors of the study. Other USF study authors were Demian Obregon, MD candidate; Huayan Hou, MD; Takashi Mori, PhD, Jin Zeng, MS; Jared Ehrhart; PhD candidate; Douglas Shytle, Ph.D; Brian Giunta, MD; and David Morgan, PhD.
The study was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Johnnie B. Byrd Sr. Alzheimer's Center & Research Institute, and the Alzheimer's Association.
Materials provided by University of South Florida Health. Note: Content may be edited for style and length.
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