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Biogen’s drug BIIB037, and several others in advanced development, focus instead on the buildup of different set of protein fragments, called beta amyloid.
“Amyloid has a relationship with cognitive decline, but if you’re looking at both of them together, tau is the bad guy,” Melissa Murray, a neuroscientist at the Mayo Clinic campus in Jacksonville, Florida, said in a telephone interview. The majority of research into the disease has focused on beta amyloid over the past 25 years, she said.
The researchers examined more than 3,600 brains from patients who died at different stages of dementia, with Alzheimer’s confirmed in almost 1,400. Measuring amyloid and tau in the brains at various stages of disease progression allowed them to conclude that it was the level of tau that predicted how quickly a person’s mental faculties had deteriorated.
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Cognitive decline typically begins when abnormal tau accumulates in the memory center of the brain –- the hippocampus. Ultimately, toxic tau accumulates in the cortex, the part of the brain involved in higher levels of thinking, planning, behavior and attention, Murray said.
Drug DevelopmentCompanies including Johnson & Johnson, Biogen and AbbVie Inc. have products in the early stages of development that target tau in the brain. TauRx Pharmaceuticals Ltd., a closely held, Singapore-based drug developer, is testing a tau-targeting compound in broader human trials.
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The Mayo Clinic study doesn’t discount the idea that beta amyloid may be involved in Alzheimer’s progression. The findings may indicate that scientists need to consider multiple approaches and targets, said Dean Hartley, director of science initiatives at the Alzheimer’s Association.
“Depending on where you are in the disease, you may need certain types of treatments,” Hartley said. “If you’re later in the disease, maybe tau is extremely important, but if we don’t want any of the clinical symptoms to develop, then maybe we want to target amyloid.”
On Friday, Biogen released early-stage clinical trial data showing that its experimental Alzheimer’s drug clearly reversed the build-up of beta amyloid in the brain and also showed signs of reducing cognitive decline. The company’s shares shot up 10 percent on the news. Analysts said the therapy, if successful in later-stage trials and approved, could become a more than $10 billion drug for Biogen and partner Eisai Co.
That’s just one amyloid-targeting therapy in trials. Eli Lilly & Co. is currently retesting its drug solanezumab in earlier-stage patients. Roche Holding AG is continuing to sponsor a trial of its amyloid-targeting drug in Alzheimer’s patients with mild dementia, though in December it abandoned a study of people with early stages of the disease because of poor results.