Berislav Zlokovic, professor and chair of the Department of Physiology and Biophysics at the Zilkha Neurogenetic Institute, led a team from the University of Rochester that found that a synthesized compound known as FPS-ZM1 can reverse inflammation and improve blood flow in the brains of mice, dramatically improving their ability to learn and think. The institute is based at the Keck School of Medicine of USC.
The research was published in early March in The Journal of Clinical Investigation.
FPS-ZM1 specifically targets Receptor for Advanced Glycation Endproducts (RAGE), a molecular vehicle on which amyloid beta peptides travel in the brain. Amyloid deposits are known to cause inflammation and obstruct blood flow in the brain.
“Unexpectedly, by blocking RAGE in brain cells, we stopped the synthesis of amyloid in the brain,” Zlokovic said. “I believe RAGE is a tremendous target for Alzheimer’s disease and that we can reduce the cognitive problems patients experience if we can utilize RAGE as a therapeutic target.”
Zlokovic was one of the first researchers to identify the role of RAGE in Alzheimer’s disease, publishing a 2003 paper on the discovery of the molecule in Nature Medicine.
The team screened more than 5,000 compounds before finding FPS-ZM1, which is significant because it can cross the blood-brain barrier.
The researchers tested the compound in older mice bred to accumulate the amyloid beta peptide quickly in their brains. After FPS-ZM1 was administered, the mice experienced a decrease of up to 80 percent in levels of amyloid beta and 80 percent less inflammation, Zlokovic said. The compound also was tolerated well by the mice.
“We tested the mice for cognition and memory, and learning and memory, and there was tremendous improvement – almost back to normal – compared to mice without the Alzheimer’s pathology,” he said.
Additional research must be done before FPS-ZM1 can be tested in humans, Zlokovic said.
The research was supported by grants from the National Institutes of Health, the Institute for the Study of Aging and the Alzheimer’s Drug Discovery Foundation.