Researchers To Test New Alzheimer’s Drug Targeting Inflammation in Humans

By | April 4th, 2019

It hasn’t been a great year for Alzheimer’s drugs—or really a great decade, even. The most recent Phase 3 trial cancellation was a study testing aducanumab, a drug that was touted as one of the most promising in recent years based on early results. But the success rate for Alzheimer’s drugs is abysmal: While cancer drugs have reached a 20 percent success rate, Alzheimer’s drugs almost never make it through the pipeline, coming in at a 99.6 percent failure rate.

Targeting a New Potential Cause of Neurodegeneration

But a team of researchers from the University of Kentucky and Northwestern University is trying to turn that rate around with a new drug that targets a different potential cause of Alzheimer’s. Most drugs have aimed to reduce or clear beta-amyloid, the protein that accumulates in toxic levels in the brains of Alzheimer’s patients. But with consistent failures of drugs targeting the so-called ‘amyloid theory,’ some scientists are beginning to question if that’s the right way to stop or slow Alzheimer’s. This team is setting its sights on a different target: inflammation.

Inflammation’s Role in the Brain

“Inflammation is normally a ‘good guy.’ It clears infections and helps heal wounds, for example,” said Linda Van Eldik, director of the Sanders-Brown Center on Aging at the University of Kentucky. “But in Alzheimer’s disease, the inflammation somehow gets out of whack. It gets too strong and sustains for too long—it’s now turned into a ‘bad guy,’ destroying the neurons that carry signals from one part of the brain to the next.”

Researchers have been searching for a way to keep the ‘good’ inflammation the body needs to heal itself while stopping the ‘bad’ inflammation that causes neuron death. When inflammation works the way it’s supposed to, it keeps the body in balance and promotes healing.

Van Eldik, along with Martin Watterson at Northwestern University, developed a drug called MW-151 to fit the bill—and now it’s ready to be tested in humans in a clinical trial.

“The pharmas have spent most of their effort on inflammation,” Van Eldik said in a video statement. “But we are focused on inflammation, which has been an understudied area.”

MW-151 blocks inflammation in the glial cells, which are like the housekeepers of the brain—they clean up waste and produce peptides that help neurons grow and survive. When the cells get too inflamed, they get out of control and kill the nerve cell rather than preserving it.

Van Eldik says the drug would be like a once-daily aspirin in that you take it once per day to prevent inflammation from getting out of control.

And while she is enthusiastic about the drug moving forward, she said that a one-target approach may not be the key to solving Alzheimer’s, which is not caused by a single issue.

“This is a very complex disease ” she cautions. “A single approach—even our approach against inflammation—may not be enough,” she said. “I think this drug it will be most effective as part of a ‘cocktail’ of drugs that target multiple mechanisms of the disease. If that worked out, boy, that would be a slam dunk.”

Both the National Institutes of Health and the Alzheimer’s Drug Discovery Foundation are funding the research to study the drug with a combined $5.5 million.

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