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Researchers on Hunt for Amyloid Annihilator
Psychiatric News
Volume 47 Number 12 page 8-17

Despite intensive efforts, the quest to find an effective treatment for Alzheimer’s disease has proven unfruitful. Yet in several clinical trials, researchers were able to reduce amyloid plaques—a hallmark of Alzheimer’s—in the brains of subjects with the disease (Psychiatric News, December 2, 2011), and results from one of three trials of experimental Alzheimer’s drugs slated to be announced later this year might be encouraging.

This was perhaps the most important news to emerge from an Alzheimer’s summit held May 14 and 15 at the National Institutes of Health in Bethesda, Md. The summit was attended by some 600 Alzheimer’s scientists from 37 states and several other countries. If an effective treatment for Alzheimer’s is ever going to emerge, it might well come from this elite corps of scientists.

The scientists cautioned, however, that if one of the three experimental drug trials does produce positive results, the results may well be tepid at best, since all three were tested on individuals with mild to moderate Alzheimer’s. The thrust now, they tended to agree, is to look for an Alzheimer’s drug that would work earlier in the disease process.

Or as one of the speakers, Paul Aisen, M.D., director of the Alzheimer’s Disease Cooperative Study at the University of California, San Diego, explained, “We are now talking about prodromal Alzheimer’s. It is a substantial step forward. But I think that we need to move even earlier than that—to people who have amyloid in their brains but no symptoms.”

Nick Fox, M.D., of University College London, added, “There may be a 15-year window when you are amyloid positive but asymptomatic.” And that, he stressed, would be the window for early intervention.

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Reisa Sperling, M.D., plans to study 1,000 people aged 70 or older who are amyloid positive with no symptoms. 

Joan Arehart-Treichel

Indeed, some planning for such early-intervention trials is already under way. For instance, Reisa Sperling, M.D., an associate professor of neurology at Harvard Medical School and director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital, reported that she and her colleagues will soon be looking for some 1,000 people aged 70 or older who are amyloid positive but without symptoms to participate in a treatment trial. “We hope to begin our trial early next year,” she said.

There are several reasons why such trials are now becoming possible, the researchers pointed out. One is because new research criteria for different stages of Alzheimer’s have been issued (Psychiatric News, June 3, 2011). Another is because amyloid plaques in the brain can now be imaged with positron emission tomography (PET). Still a third is because cerebrospinal fluid levels of amyloid can now be measured. David Bennett, M.D., director of the Rush Alzheimer’s Disease Center at Rush University, reported that he and his colleagues are working on the validation of such biomarkers, which should help enable trials in asymptomatic subjects.

But even if biomarkers are validated, they will need to be standardized, Clifford Jack, M.D., Ph.D., a professor of Alzheimer’s disease research at the Mayo Clinic, pointed out—that is, scientists need to determine at what level biomarkers are normal and at what level they are abnormal. Only then, he explained, can subjects be diagnosed and categorized at different stages of disease, and only then, perhaps, can an effective treatment for Alzheimer’s be found.

A similar scenario took place in multiple sclerosis research 12 years ago, noted Christopher Lipinski, Ph.D., an adjunct faculty member at the University of Massachusetts and a medicinal chemist. Thanks to the identification of biomarkers, it became possible, for the first time, to diagnose the stage of disease in multiple sclerosis patients, and such identification in turn paved the way for the development of drugs for the disease.

Meanwhile, other promising leads toward an effective Alzheimer’s treatment were announced by Francis Collins, M.D., Ph.D., director of the National Institutes of Health (NIH).

For example, a drug was recently found that can remove amyloid plaques from the brains of mice within 72 hours. NIH has given the green light to major studies to determine whether an insulin nose spray can counter memory loss in subjects with mild cognitive impairment. Actually research suggesting that such a tack might work has been building for a few years now (Psychiatric News, December 3, 2004). “We are excited about it,” Collins said.

Still other encouraging findings—that have more to do with Alzheimer’s prevalence than treatment—were reported by Kenneth Langa, M.D., Ph.D., associate director of the Institute of Gerontology at the University of Michigan. Some studies have suggested that there might be a declining risk in age-specific dementia in the United States. If this is the case, then it might be because low educational attainment is a risk factor for Alzheimer’s, and Americans have become better educated over the past 30 or 40 years. Or it might be because more Americans are now being treated for high blood pressure—another Alzheimer’s risk factor—than used to be the case. inline-graphic-1.gif

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Reisa Sperling, M.D., plans to study 1,000 people aged 70 or older who are amyloid positive with no symptoms. 

Joan Arehart-Treichel

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