A Cancer Drug Reverses Alzheimer’s Disease in Mice

Mice are not men, so let's not get too excited yet, but scientists have discovered that an existing cancer drug quickly reverses Alzheimer's symptoms in rodents.

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Researchers at Case Western Reserve University have discovered that a drug currently used to treat cancer patients can reverse the cognitive deficits related to Alzheimer’s disease in mice, and what’s more, it accomplishes this feat in a remarkably short period of time.

The drug, called bexarotene, has been approved for the treatment of a type of skin cancer since 1999. In the new experiments with genetically engineered mice, the drug quickly cleared away the beta-amyloid plaques in the brain that are believed to cause cognitive deficits in Alzheimer’s disease.

This is not the first time that scientists have essentially cured Alzheimer’s in rodents. A decade ago, scientists got excited when a potential Alzheimer’s vaccine appeared to chew up nerve-destroying amyloid protein deposits in animal brains, but were equally disappointed when it failed to do the same in human patients.

Researchers raised hopes again when they found that an enzyme, gamma secretase, effectively suppressed the formation of amyloid — the naturally occurring protein becomes problematic when it isn’t cleared away quickly enough — in the brains of mice with Alzheimer’s-like disease. But last year Eli Lilly shut down its work on the compound when the first human patients treated with the enzyme in a trial failed to show improvements in cognitive function. In fact, they showed worse declines than those given a placebo.

In other words, the results of studies testing new medical ideas in mice should be met with skepticism, regardless of how compelling they may be. Mice, after all, are not men, and while almost every groundbreaking new treatment in people begins with animal trials, not every mouse study results in a life-changing therapy.

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So with that in mind, let’s take a look at what the Case Western scientists reported in Science. Instead of working at the front end of the amyloid problem — in other words, trying to shut down its production — Gary Landreth and his team focused on the trying to improve ways of ferrying amyloid out of the brain. The body has a built-in way of doing this, relying on proteins called ApoE, which remove fats, including cholesterol, and amyloid from the brain.

After nearly a decade studying these natural clearing mechanisms, Landreth focused on a class of receptors on cells that help them engulf and remove amyloid like hungry molecular sinkholes. Fortunately, the pharmaceutical industry had already developed a drug that facilitated this process: the cancer drug bexarotene.

When Landreth’s graduate student, Paige Cramer, injected the drug into mice with Alzheimer’s-like symptoms, they showed a rapid reversal in their brain abnormalities. Within 24 hours of getting the drug, the mice showed a 25% drop in amyloid in their brain fluid; after two weeks, they had a 75% decline in the sticky plaques formed by amyloid.

The drug also restored the animals’ normal behaviors. After treatment, the mice could build a nest, identify a smell and perform better on water maze tests requiring them to remember how to find a submerged platform. They were also better able to remember a cage in which they had been shocked.

“The effect size and the speed seen with the drug is unprecedented,” says Landreth, “and it gives us all hope.”

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That doesn’t mean that Alzheimer’s patients should be asking their doctors for a prescription of bexarotene just yet. The mouse model of Alzheimer’s isn’t perfect. Mice don’t get Alzheimer’s the same way humans do. They build up amyloid protein in the brain, and those deposits form plaques that disrupt nerve function and affect learning and memory, just like they do in Alzheimer’s patients; but in mice, there is no progressive worsening of the condition resulting in the destruction of nerve fibers. Humans lose brain cells and suffer the buildup of detritus from a dying neural network.

So it’s not clear yet whether bexarotene would have the same effect in an Alzheimer’s brain in which some of this destruction is already established. “I want to loudly and clearly say that this work has been done in mice,” says Landreth. “Let’s be very cautious in extrapolating forward to humans. We’ve fixed Alzheimer’s disease in mice a lot, and the translation to humans has been imperfect; in fact, it’s failed.”

Even so, says Dr. Mary Carrillo, senior director of medical and scientific relations at the Alzheimer’s Association, the fact that bexarotene appears to be working at the earliest stages of the disease, and possibly even preventing it from progressing, is very tantalizing. “The clearance of a-beta [amyloid] happens earlier than what we saw with the vaccine,” she says. “And it suggests the intriguing idea that we might be able to interrupt the accumulation of amyloid with earlier clearance and can potentially allow less damage to occur in the brain.”

That would require being able to identify Alzheimer’s patients at the very beginning of what’s been called their long goodbye. And that’s not easy. The most recent studies hint that the build up amyloid and the destruction of nerve cells begins decades before patients show signs of memory loss or other cognitive changes, and pinpointing those early stages of the disease requires more sophisticated ways of tracking either amyloid or physical changes in the brain with imaging techniques. Scientists are making headway in doing just that, and the latest revisions to diagnosing Alzheimer’s, as well as it’s precursor state, mild cognitive impairment, reflect the growing emphasis on these initial stages of the disease. But the line is still fuzzy, and researchers continue to debate the distinction between aging-related senior moments and the first lapses in memory that signal Alzheimer’s dementia.

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But if the mouse work translates to people — trials of bexarotene in healthy humans may begin in a few months, but experiments in those with Alzheimer’s would be years away — it could mean the first therapy that could potentially reverse the initial pathological steps of Alzheimer’s. That would certainly go a long way to preventing millions of patients from descending into cognitive decline.

Alice Park is a writer at TIME. Find her on Twitter at @aliceparkny. You can also continue the discussion on TIME’s Facebook page and on Twitter at @TIME.

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