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Researchers seek to short-circuit Alzheimer’s

Drug intended to stop disease before it starts to be tested

Arthur Canter, 67, of Mattapoisett, is among those enrolled in the groundbreaking drug trial.Jessica Rinaldi/Globe Staff/Globe Staff

The radio ad pierced Helene DeCoste’s thoughts as she drove home from an exhausting day in Lexington, clearing out mountains of paperwork in her older sister’s house. Bills and documents had piled up as her sister sank into a fog of dementia.

Boston researchers, the radio ad said, sought volunteers to test an Alzheimer’s drug. DeCoste, who watched her mother die of Alzheimer’s and is witnessing the same decline in her 73-year-old sister, dialed the study number soon after she got home.

The researchers, it turned out, were seeking participants exactly like DeCoste for their landmark study — the first medical trial to test whether a drug can prevent Alzheimer’s disease in people who have no symptoms but are at risk.


“I am just not good asking people for money” for research, said DeCoste, a 67-year-old retired teacher from Abington. “But this, I can do.”

DeCoste is among the first volunteers in the study, called A4, that aims to enroll 1,000 adults, 65 to 85 years old, in the United States, Canada, and Australia. The study’s 60 research centers include two in Massachusetts, Boston University and Brigham and Women’s Hospital.

There is no promise that the drug will work in staving off a brain-robbing disease that afflicts 5 million people in the United States — a number projected to almost triple by 2050. But for people such as DeCoste and Arthur Canter, a 67-year-old retired executive from Roslindale who is also enrolled, the trial offers a chance to fight back against an incurable disease.

“A lot of people fear the unknown, but if we just sit back and don’t do anything, if you don’t confront it, the issue never gets resolved,” said Canter, whose mother has Alzheimer’s and whose father had dementia. “I feel like I am doing something that is going to impact this awful disease.”

Alzheimer’s drug trials have a long and disappointing track record, with many failing to prove effective.

But results released last week from another Alzheimer’s study bolstered hopes. Initial findings showed that an experimental drug from Cambridge biotech company Biogen reduced the levels of abnormal proteins in the brain called amyloid plaques, believed to be markers for the disease. The improvement was seen in a small group of patients who already have mild memory and thinking impairments, and that reduction correlated with a slowing of their mental decline.


A different experimental drug — solanezumab, made by Eli Lilly and Co. — has been selected for the A4 trial. The drug failed to produce significant improvements for patients in a large 2012 study. But a closer analysis found that some of the patients with very early stages of Alzheimer’s did show modest improvements.

That’s why A4 participants must not yet have the thinking and memory problems associated with Alzheimer’s, but have an elevated level of the telltale amyloid plaques, revealed by scans. Researchers believe the plaques build up in a person’s brain years before symptoms appear. And they suspect the key to beating Alzheimer’s is to clear out the amyloid before symptoms appear and brain cells have been damaged — much the same way patients with high cholesterol are given statin drugs to head off cardiovascular problems.

Given her family history, DeCoste said she has long feared the specter of Alzheimer’s.

“It’s always been on my mind,” she said. “When my sister started showing symptoms, and then was diagnosed with mild cognitive impairment, I felt I had to be proactive for me, and also for her.”

Helene DeCoste, 67, got her study medication intravenously infused Thursday as she participated in an Alzheimer’s study at Brigham and Women’s Hospital.JESSICA RINALDI/GLOBE STAFF/Globe Staff

The study requires participants to visit a research center once a month for three years, where half will receive the drug, and the others will receive a placebo — a substance that looks like the drug, but is inactive. Both are given intravenously, and the participants are not told which they receive.


Researchers are tracking memory and thinking declines in both groups, and using brain scans to measure whether those changes correspond to their amyloid levels to determine if the drug works.

About half of the participants will also receive scans to track build up of another protein, tau, that forms toxic tangles in Alzheimer’s patients, killing brain cells.

Tau is commonly found in small amounts in people over 65, but researchers believe tau is unleashed when it encounters amyloid, which acts like an accelerant, said Dr. Reisa Sperling, a Harvard Medical School professor who is leading the A4 study.

“Amyloid pulls the trigger, but tau is the bullet,” Sperling said, repeating a phrase coined by her husband, Dr. Keith Johnson. Johnson is leading the tau imaging for the A4 study, and is director of molecular neuroimaging at Massachusetts General Hospital.

The A4 study has enrolled about 100 participants, and some of the centers are struggling to attract a racially and ethnically diverse group of volunteers. The goal is to fill 200 of the 1,000 slots with people of color.

“We need to come up with additional efforts, thinking outside the box, to reach people of all ethnic groups,” said Sperling, who directs the Alzheimer’s research and treatment center at the Brigham.


One significant hurdle was designing a test to detect subtle changes in memory and thinking for Spanish-speaking participants. Researchers learned that certain words or concepts may be interpreted differently by Hispanic participants in California from Mexican descent, compared to those from New York with Puerto Rican lineage.

While the researchers hunt for more volunteers, other scientists are exploring different approaches for preventing Alzheimer’s. But they are not abandoning the search for drugs to treat patients already in the throes of the fatal disease, said Laurie Ryan, who oversees Alzheimer’s trials funded by the National Institute on Aging.

The federal agency contributed $36 million toward the A4 study, which also received support from the maker of solanezumab, Eli Lilly and Co., and several philanthropic organizations.

For Sperling, the A4 study is a mission. While she was in medical school three decades ago, her grandfather developed dementia, and watching him fade away convinced Sperling to make Alzheimer’s research her life’s work. Sperling vowed she would find a cure before its tentacles ensnared her father.

But the disease got there first. Leslie Sperling, an 82-year-old college chemistry professor in Pennsylvania, was diagnosed with Alzheimer’s about a year ago.

“I feel like I failed,” Reisa Sperling said. “Alzheimer’s disease is a war, and we are losing, but I am going after it with two fists next.”

For more information: A4STUDY.ORG. (617) 278-0379.


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Kay Lazar can be reached at Kay.Lazar@globe.com.