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Alzheimer’s Research Seeks Earlier Detection

BOSTON — In the last decade scientists have launched several large-scale clinical trials for what were considered promising new drugs to treat Alzheimer’s disease. But as of yet there is nothing on the market that halts or even slows down the progression of Alzheimer’s in patients.

Some of these trials were stopped early because of patient deaths or dangerous side effects. Other studies failed because the drugs were considered altogether ineffective.

Most of the trials focused on therapies that reduce amyloid in the brain. Amyloid is a protein that builds up in the brains of Alzheimer’s patients and causes brain damage.

‘I’m Aware That I Am A Guinea Pig’

Devora Corman is a 77-year-old Alzheimer’s patient who is currently testing an anti-amyloid drug. It wasn’t long after she was diagnosed with the disease that Corman, a painter, stopped doing her art.

“I really miss my painting,” she says. “But I get frustrated so I stop.”

The first trial Corman was on was helping her, according to her daughter, Julie Corman. “I remember when she was on that drug she said she would have days that were less cloudy,” she says.

New diagnostic tests are revolutionizing Alzheimer’s research. Lab tests can now determine whether people who have no symptoms at all may develop the disease later.

But Corman stopped that drug because several people in the study died. That did not deter her from enrolling in another experimental trial, however, and she’s now enrolled in another study of an anti-amyloid drug.

“I’m aware that I am a guinea pig but I think that’s a good thing,” she says. “It helps me and it helps the rest of the world.”

In many ways, Corman — an older woman with Alzheimer’s — is a typical study subject. But that may be changing.

Toward ‘Prevention Studies’

Many scientists believe that one of the reasons that past drug trials have been ineffective is because the patients tested already had too much damage to their brains to benefit.

“By the time people have mild to moderate dementia they have lost 50 to 70 percent of key nerve cells in the brain critical to memory,” says Dr. Reisa Sperling, director of the Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital in Boston.

“So even if we are able to successfully suck all the amyloid out of the brain it is unlikely we can regrow all the nerve cells and connections to make people what they were five or 20 years before,” she says.

Scientists once believed that a diagnosis of Alzheimer’s came when a patient had symptoms. Now the thinking is that, like cancer and heart disease, Alzheimer’s may develop for decades before a person experiences any memory loss or other problems.

New national guidelines (PDF) were introduced last summer that stress the early diagnosis and treatment of Alzheimer’s disease. With this in mind, scientists are now recruiting patients that do not yet show signs of the disease but have signs of amyloid in their brain. And new diagnostic tests are revolutionizing Alzheimer’s research. Lab tests can now determine whether people who have no symptoms at all may develop the disease later on.

Researchers are recruiting patients for new “prevention studies.” The idea is to test people pre-symptomatically and see if a drug protects them from getting Alzheimer’s.

These new studies are a challenge.

Julie Corman, the daughter of Alzheimer’s patient Devora Corman, says she would not enroll in one of the prevention trials. She would worry too much.

“No, I would not be tested,” she says. “I do not want to know what the future holds.”

Dr. Dennis Selkoe, of Harvard Medical School, understands this sentiment.

“A lot of patients don’t want to be on an experimental drug for four years, especially when they have no symptoms,” he says. “That’s a challenge compared to giving someone who already has symptoms of the disease an 18-month trial and measuring the rate of decline. But just because it’s challenging doesn’t mean we shouldn’t do it.”

Other Research

Another new frontier is research into tau. Tau is another protein that builds up in the brain of people with Alzheimer’s and may assist amyloid in causing more destruction, according to Selkoe.

“Tau is very important for amyloid to do its dirty work — if tau is lowered or removed in some way there’s not as much damage from amyloid beta,” he says.

So far the tau studies have been fairly preliminary, but Selkoe believes human trials will begin soon.

Many scientists are also studying the role of inflammation in Alzheimer’s and whether diabetes and cholesterol are risk factors for the disease.

Others researchers are studying which genes may cause symptoms in Alzheimer’s patients and how understanding those genes may lead to new treatments.

Dr. Li-Huei Tsai, director of MIT’s Picower Institute for Memory and Learning, studies mice with symptoms of Alzheimer’s. Tsai says she has developed a compound that can restore the mice’ ability to remember.

“This chemical can somehow enhance the expression of all genes necessary for learning and memory,” she says.

The next step is human trials, which Tsai hopes to begin in the next few years.

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