Alzheimer's: Beyond Stem Cells

From Wired Jun. 11, 2004 PT

Despite the high profile that Nancy Reagan and others have given the idea of using embryonic stem cells to treat Alzheimer's disease, advances are likely to come faster from other approaches.

Experts cite other more promising efforts that in five to 10 years may be used to fight the disease that led to President Reagan's death. "I just think everybody feels there are higher priorities for seeking effective treatments for Alzheimer's disease and for identifying preventive strategies," said Marilyn Albert, a Johns Hopkins University researcher who chairs the Medical and Scientific Advisory Council of the Alzheimer's Association.

Stem cells from human embryos can form all types of cells, and the hope is that they one day could be used to replace cells damaged from such conditions as diabetes, spinal cord injury or Parkinson's disease. But experts say Alzheimer's, by the very nature of how it attacks the brain, would pose a far more daunting challenge to that approach.

"There's an awful lot going on right now that perhaps holds a little bit more immediate promise for trying to slow the disease, or even cut off its development," said Marcelle Morrison-Bogorad, associate director of the National Institute on Aging's neuroscience and neuropsychology of aging program.

She and Albert cited, for example, efforts to attack the buildup of clumps of protein called amyloid in the brain, and methods for spotting the disease early. That research will probably pay off in five or 10 years, earlier than any expected advances from stem cells, Albert said, because so much has to be learned about how to make stem cells useful against the disease.

"All the more reason we should start (stem cell efforts) now, because it's going to take a long time," she said.

About 4.5 million Americans have Alzheimer's, a progressive brain disorder that gradually destroys memory and ability to learn, reason, communicate and do everyday activities. Patients die on average eight years after symptoms appear, although the disease can linger for 20 years.

"What you're dealing with here is a mind in disarray," Morrison-Bogorad said. Connections between brain cells are being lost, neurons are dying and becoming dysfunctional, the amyloid plaques are building up between brain cells, and protein tangles are showing up within cells. And there's inflammation.

"It's just a mess in there," she said. "But the mess means there are so many targets for intervention."

The amyloid plaques have emerged as a favorite target, and scientists and drug companies around the world are studying ways to prevent or destroy them.

One high-profile approach is a vaccine that primes the body to attack amyloid. Studies on animals were encouraging, but in 2002 a study on people was halted when several vaccine recipients developed brain inflammation. Last year, researchers reported that the vaccine did appear to reduce the accumulation of plaques in one study participant.

Work is continuing now on a safer vaccine, because the available evidence suggests "this is an important avenue to pursue," Albert said.

Another popular approach seeks to keep the brain from making the abnormal form of amyloid that creates the plaques. It's a high priority at "every major drug company," Albert said.

The overall focus on amyloid makes her optimistic.

"Everybody's working on it," she said. "What we've learned from the past is that if everybody works really hard at something that is sensible, they're likely to make a lot of progress. So there's just enormous optimism that in five years, or certainly 10 years, we'll have much more effective treatments."

Another key research area is finding a way to predict who will get Alzheimer's before symptoms appear. Because the disease develops over many years, much damage has been done by the time it's diagnosed. So scientists want to identify people at an earlier stage for the day when more effective treatments become available.

In the same vein, scientists want to find ways to track the progress of the disease in people being treated, so they can quickly tell if the treatment is helping.

So researchers are doing long-term studies to see if different kinds of brain scans, mental tests and spinal or blood tests can predict development or progression of the disease.

Lifestyle factors too, such as taking anti-inflammatory drugs and vitamins like E and C, are being studied to see if they can help prevent Alzheimer's or delay it.

Researchers are also exploring the use of cholesterol-lowering drugs. A relatively recent idea, Albert said, is that things like keeping cholesterol and blood pressure low and staying physically active may help. Those steps are well-known for countering heart disease, she noted.

But it's becoming clearer, she said, that "if you do things that are good for your heart, they'll be good for your brain."

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