Another Run at Targeting RAGE

One of the underlying mechanisms by which the advanced glycation endproducts (AGEs) that build up with age cause harm is through hammering on the receptor for AGEs, or RAGE. Some Alzheimer's researchers are looking into targeting RAGE in order to remove the contribution of AGEs to that condition, and it is possible that the results of their work may have more general application to AGEs in aging - though the best possible strategy would be to remove the AGEs rather than work around them: "Researchers have taken another crack at a promising approach to stopping Alzheimer's disease that encountered a major hurdle last year. ... scientists have developed a compound that targets a molecular actor known as RAGE, which plays a central role in mucking up the brain tissue of people with the disease. Scientists [synthesized] a compound that stops RAGE in mice - reversing amyloid deposits, restoring healthy blood flow in the brain, squelching inflammation, and making old, sick mice smarter. But the scientists caution that the work has a long way to go before it's considered as a possible treatment in people. ... A phase 2 study in 399 people of another compound designed to stop RAGE - which stands for Receptor for Advanced Glycation Endproducts - was halted prematurely in November when scientists had questions about the compound's safety at high doses, and after early results indicated that the compound was not helping patients with Alzheimer's disease. ... The benefits of blocking RAGE are even greater than has been realized. RAGE is central to many mechanisms that wreak havoc in the brains of people with Alzheimer's disease. It turns out that when you inhibit RAGE, you block molecules central to creating inflammation in the brain, and that is a major problem with Alzheimer's disease."



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