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Health

Alzheimer's protein may be cancer's treatment

It is unknown whether amyloid is a cause or byproduct of the brain disease. But research shows it could double as a tumor killer.

By STEPHEN NOHLGREN, Times Staff Writer
Published June 19, 2004

SARASOTA - A protein found in the brains of Alzheimer's victims may someday fight cancer by starving tumors of their blood supply, scientists from Sarasota and Tampa announced Friday.

Full-scale use in humans is probably five years away, if ever. But researchers view early reports as encouraging.

The protein - called amyloid - shrinks human brain and lung cancers that are injected into lab rats. It reduces the development of new blood vessels, which are critical to tumor growth.

"This is very exciting. As researchers, this is what we live for," said Steve Brem, director of the brain tumor program at Tampa's H. Lee Moffitt Cancer Center, who addressed a news conference with a mixture of sober caution and barely restrained enthusiasm.

"There are still a lot of hurdles here. Many things that work out in the lab don't pan out," Brem said. For example, amyloid could prove toxic to patients. "But the idea that something could be the villain in one disease and the hero in another is a great story."

Amyloid has long been a prime suspect as a possible cause of Alzheimer's disease. Autopsies show abnormal clumps of amyloid next to decimated brain cells. Amyloid also surrounds blood vessels in an Alzheimer's brain, and those blood vessels are smaller than normal.

About 18 months ago, researchers at Sarasota's Roskamp Institute were surprised to discover that amyloid retards the development of blood vessels.

"We expected exactly the opposite," said Roskamp scientist Daniel Paris, an Alzheimer's specialist. Brain inflammation is a tell-tale sign of Alzheimer's, and usually inflammation is associated with more blood vessels, not fewer, Paris said.

The discovery led the Roskamp group to quickly shift its focus. Combating blood vessel growth is a hot trend in the cancer fight. Drug manufacturers all over the country are searching for compounds that can cut blood supplies. The Food and Drug Administration recently approved the use of one such drug, Avastin, which has doubled life expectancies for people with colon cancer, Brem said.

Lab tests at Roskamp showed that amyloid significantly hampered the growth of blood vessels in rat corneas and chicken eggs. It also retarded the growth of human arterial tissue.

So Roskamp, the Alzheimer's people, forged a partnership with Moffit, the cancer people, for more exhaustive tests. They injected human lung and brain cancers into rats. When the tumors reached 150 square millimeters - pea sized - some of the rats were injected with amyloid.

The tumors kept growing in the rats that didn't get the amyloid. In the rats that got the amyloid, lung tumors shrank an average of 60 percent and brain tumors an average of 50 percent, Paris said.

Okay, but do people really want injections of a protein that might cause Alzheimer's?

The causal relationship between amyloid and dementia is still unknown, Brem and Paris said. Maybe amyloid is a byproduct of the disease, not the cause. For years, scientists tried to give Alzheimer's to lab rats by injecting them with large quantities of amyloid, and it never worked. It took genetic engineering to create the first rat with Alzheimer's disease.

People with brain cancers, particularly, might benefit if amyloid proves effective at starving tumors. Amyloid already exists naturally in the brain. And primary brain cancer is such a fierce, lethal disease that its victims might be more willing than people with other cancers to serve as amyloid guinea pigs.

Before that can happen, the scientists expect to spend several years testing amyloid. At what point will it be toxic? Can small pieces be effective, which will reduce production costs and make it easier to deliver as a drug?

If all goes well, rats will get the first tests, then small groups of humans.

Brem emphasized that any human trials are years away. "We have families who have just got a bad diagnosis and we have to be compassionate," he said. "But we don't want them calling us and saying "Where can I get this molecule?' "

Roskamp and Moffitt will continue as a team, the scientists said, but they also need money from government agencies or drug manufacturers - hence Friday's news conference, which was designed to generate nationwide interest.

ALZHEIMER'S-CANCE R LINK?

WHAT IS IT? Scientists say a protein associated with Alzheimer's disease shrinks tumors by reducing blood supplies.

WHAT COMES NEXT? Tests must determine if the protein is safe and suitable for use as a drug. Rats would be tested first, then small groups of humans.

WILL IT WORK? No one knows. Even if everything goes right, full-scale use on humans wouldn't begin for at least five years.

[Last modified June 18, 2004, 23:55:17]


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