Latest anti-RAGE compound defeats Alzheimer's symptoms in mice

A team of scientists from New York, California and elsewhere believe that they have another shot at stopping RAGE, which would be a major win in the battle against Alzheimer's disease.

RAGE (receptor for advanced glycation endproducts) is a receptor that scientists believe leads to brain inflammation and helps contribute to the growth of amyloid deposits in the brain. But the researchers from the University of Rochester Medical Center in upstate New York and the University of Southern California led an effort to develop a potential new drug that stops RAGE's activity in mice. Results were promising, with the compound causing the amyloid deposits in the brain--a telltale sign of Alzheimer's--to deplete. Also, blood flow improved, and the elderly mice became healthier. The drug--FPS-ZM1--apparently was also quite effective at crossing the blood-brain barrier.

So what previous effort to stop RAGE failed? The researchers themselves note indirectly in their announcement that scientists running a Phase II trial testing a similar compound against RAGE stopped their work abruptly in November over safety concerns at high doses and data suggesting that the compound wasn't working for Alzheimer's patients. According to the Alzheimer Research Forum, this was a drug sponsored by Pfizer ($PFE).

Why might this drug eventually be more effective than the Pfizer one? Benjamin Miller, a biochemistry and biomedical engineering professor at the University of Rochester, told FierceBiotechResearch via e-mail that is too early to tell. But he pointed out that, so far, the compound doesn't appear to have created any toxicity in mice, even at high doses.

"And if we can demonstrate that this low toxicity translates to humans--and of course that's a big 'if'--that will open up major opportunities for increasing the dosage and potentially increasing the drug's effect," Miller said.

Of course, this compound showed promise in mice. It will be some time before researchers will know if the drug works in people, and there will be many more years of trials at the preclinical stage before they even reach that point. But it's not for lack of trying. As the study announcement points out, lead researcher Berislav Zlokovic--based at USC--is a founder of a company called Socratech, which is testing treatments for Alzheimer's and other neurodegenerative diseases. For more details on the RAGE study, read The Journal of Clinical Investigation online.

- here's the release
- read the study
- check out the Alzheimer Research Forum for added background