Scientists should soon launch another assault on the steep slopes of Alzheimer’s disease, if new genetic research by Seattle investigators pans out as hoped.

Seattle-based researchers from Merck have identified a gene important in production of the sticky protein that clogs the brains of Alzheimer’s patients.

“If we can block the action of this gene, we could have a potential therapeutic,” said Dr. David Stone, lead scientist of the research conducted over three years at Merck’s laboratories in the South Lake Union area.

The protein, called amyloid beta, is believed to be a major factor in Alzheimer’s. It binds to brain cells, killing them and impairing memory, reason and the ability to move and speak.

The gene found by Stone and his colleagues is important in the way cells use an enzyme to cut a larger protein to form amyloid beta. The scientists aren’t exactly sure how the gene works. But when they stopped its action in human cells in the laboratory, they found it reduced production of the toxic amyloid beta by about half.

The gene is believed active in the form of Alzheimer’s disease that begins later in life, after age 65. Most of the genetic research has been on a form that affects younger people.

The Merck researchers are especially enthusiastic about the discovery because the gene is on a chromosome previously linked to Alzheimer’s, though no one knew why. And it is active in parts of the brain known to be susceptible to the disease.

“It’s an excellent candidate gene [for a drug] at this point,” said Stone, who is now based at Merck’s West Point, Pa., laboratories. The research is reported in this week’s online edition of the Proceedings of the National Academy of Sciences.

About 4.5 million people in the U.S. have Alzheimer’s disease. But researchers believe that as the population ages, that could grow to 16 million by 2050.

Just last week, the 100th anniversary of the identification of the disease by Alios Alzheimer was observed in Tubingen, Germany. Scientists from around the world gathered to discuss both the earliest and latest findings about the disease.

Drugs now approved to treat the disease slow symptoms, but they

typically are effective for only a few years. Another drug, made by Eli Lilly, is now being tested in humans. It is designed to stop production of an enzyme important in amyloid beta production.

Stone said the Merck team is now observing how amyloid beta production is affected in mice when the gene is removed. He said it is difficult to know when a drug could be developed and when testing it could begin in humans. If all goes well, it would be at least five to seven years before a new drug could be on the market.

The Seattle researchers screened more than 15,000 genes before finding the one they’re pinning their hopes on: Leucine Rich Repeat Transmembrane 3. They used a technique that actually blocked the gene’s activity to learn its function.

Stone said the gene appears to be active only in the brain, so a drug acting on the gene is not likely to affect any other part of the body, he said.

Dr. Gerard Schellenberg, a geneticist at the Veterans Affairs medical center in Seattle, said the Merck-discovered gene may well have promise as a drug target.

The Merck research is “pretty convincing evidence that the gene affects one of the proteins that helps make the bad stuff, amyloid beta,” said Schellenberg, who discovered an Alzheimer’s gene in 1995 and just returned from the 100th anniversary observance in Germany.

Attribution: Seattle Times

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