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Trials of beta amyloid inhibitors fail to show improvements in Alzheimer's patients


By Sabriya Rice
Posted: January 23, 2014 - 7:00 am ET
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Hopes for effectively treating Alzheimer's patients took another hit Wednesday, as new studies found that two once-promising drugs failed to improve patient cognition during Phase 3 clinical trials.

The two beta amyloid inhibitors, solanezumab and bapineuzumab, both failed to achieve improved cognition in patients with mild to moderate Alzheimer's disease, according to two new studies in the New England Journal of Medicine published Wednesday. The authors and other experts on Alzheimer's say research into beta amyloids should continue despite the disappointment.

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One study suggested that future research should focus on use in patients in the years before the onset of symptoms. “Initiation of the antiamyloid treatment only after dementia develops may be too late to affect the clinical course of the disease,” wrote the authors of the study on bapineuzumab.

“I don't think we should be distraught or discouraged, because the research in this area has dramatically changed how much we know and how we treat people,” said Dr. Eric B. Larson, vice president of research for Group Health Research Institute in Seattle. At the same time, he said, researchers and clinicians should not put all their hopes in any drug. “To think that targeting a single abnormal protein is the only way, or even an effective way, to deal with this disease may be na´ve and simplistic. You'll continually be disappointed.”

In a NEJM perspectives article last year, Larson urged greater attention to lifestyle interventions that can affect the onset of Alzheimer's disease, such as improving cardiovascular health and reducing the risk of diabetes.

Alzheimer's is an urgent problem, said Dean Hartley, director of science initiatives for the Alzheimer's Association. There are currently more than 5 million Americans with the disease, and that number could jump to 16 million by 2050. The Alzheimer's Association said the Obama administration's recent appropriation of $122 million towards Alzheimer's research, education, outreach and caregiver support will help.

“We need a broad portfolio of research that not only looks at plaques and tangles in the brain but at the multiple risk factors that may impact Alzheimer's,” Hartley said. “The only way we are going to find answers is through research, and we still don't have enough dollars going toward this disease.”

Alzheimer's disease is a neurodegenerative disease in which proteins called beta-amyloids and tau clump together in the brain, eventually forming large plaques and tangles that block the nerve cells from signaling and functioning properly. Development of these plaques and tangles is thought to be a pivotal factor in promoting cell death and eventually leading to progressive dementia.

Drug manufacturers have created or are developing therapies that bind to amyloids, such as beta-amyloid or tau proteins, so they don't continue to form abnormal clumps of protein in the brain, with the hopes of maintaining or improving cognition and functional abilities in patients.

Follow Sabriya Rice on Twitter: @MHsrice


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