An $80 million national research plan to attack Alzheimer’s, a mind-robbing malady that may affect as many as 16 million Americans by 2050, will start this year with U.S.-sponsored studies on ways to prevent the disease in high- risk people, and treat it with an insulin nasal spray.
The National Institutes of Health will spend $7.9 million testing the spray, and $16 million on the first study to focus on growth of the disease in high-risk patients, the Health and Human Services Department said today. The study in those most likely to get Alzheimer’s will be run by Roche Holding AG (ROG), using the Swiss company’s experimental drug crenezumab.
The goal, to develop new treatments by 2025, faces tough challenges, said Ronald Petersen, a researcher at the Mayo Clinic in Rochester, Minnesota. Researchers aren’t sure what sets off the disease process that leads to dementia or whether protein tangles in the brain -- a disease hallmark -- are a cause of the condition or a byproduct.
“This represents a blueprint for dealing with this crisis,” Petersen said in an e-mail. “Now the challenge begins to implement it to make major advances in research and care for patients with Alzheimer’s disease.”
The plan is part of the National Alzheimer’s Project Act, signed into law last year. About 5.4 million Americans have the disease now, according to the Centers for Disease Control and Prevention in Atlanta.
The Roche-partnered study will test crenezumab, also known as RG7412, in about 300 people in Colombia with a genetic mutation that leaves them nearly certain to develop Alzheimer’s in their 40s. If the drug works, researchers plan to expand the tests to people who don’t have the mutation and yet are still at high risk of developing the disease later in life, said Pierre Tariot, director of the Banner Alzheimer’s Institute.
“It is possible that we would identify ways to predict who is at risk for late-onset Alzheimer’s disease,” Tariot said in a telephone interview. “It’s at least theoretically possible that prevention therapy could be identified that is so safe it could be given to anybody, because remember that age itself is a major risk factor.”
Crenezumab attacks beta amyloid, a protein that builds up in the brains of Alzheimer’s patients. Therapies targeting the protein haven’t been successful yet, though, with failures including Eli Lilly & Co. (LLY:US)’s semagacestat in 2010.
This Colombian study will take a different tack, attempting to prevent the buildup of amyloid before Alzheimer’s symptoms appear, Tariot said. It could be the best test yet of the amyloid hypothesis, he said.
“The amyloid accumulates over years and years,” said Richard Scheller, chief scientific officer of Roche’s Genentech unit, which is working on the drug. “By the time one is showing signs of dementia, there has already been damage to the brain. Once the brain circuitry is unravelling, it may be difficult to stop it.”
Roche expects results next year from mid-stage tests of crenezumab in patients with mild to moderate Alzheimer’s, Scheller said. The Colombian trial will help provide the basis for deciding whether to test the drug in the broader population of people at risk for Alzheimer’s, he said.
“Breakthroughs leading to treatments have been slow in coming,” Kathleen Sebelius, secretary of the HHS, said at a conference on the disease in Bethesda, Maryland, today. “Clinical trial results continue to be disappointing. We’ve yet to find treatments or ways that are proven to prevent Alzheimer’s, and that’s the ultimate goal.”
The HHS also announced plans to provide more training for health-care providers and information for caretakers, as well as a new awareness campaign that will include television advertising.
Alzheimer’s destroys brain cells, making it difficult for patients to think, remember and function. Markers of brain cell death include amyloid plaques and tau tangles that can begin in the brain 10 to 20 years before symptoms occur.
Researchers suspected a link between Alzheimer’s disease and diabetes after scientists found excess insulin in the blood was associated with the diseases later in life. Insulin is known to help maintain the brain’s synapses.
A 2010 study found that people with early stages of the disease who used an insulin inhaler made by Kurve Technology Inc. twice a day showed improved ability to carry out daily tasks, like dressing or balancing their checkbook.
Previous studies show diabetics have an elevated risk of developing Alzheimer’s disease and mild cognitive impairment, a potential precursor to the most common form of dementia in the elderly. Catching the disease early when memory and language deficits first develop may improve the odds of treating the condition or preventing it altogether.
Efforts to capitalize on the link have yielded mixed results. A daily dose of inhaled insulin improved the memory of patients with early-stage Alzheimer’s and helped them manage routine tasks like getting dressed. The approach didn’t improve other measures of mental function. GlaxoSmithKline Plc (GSK:US)’s Avandia, once the biggest selling diabetes drug, failed to benefit Alzheimer’s disease patients in a 2009 study.
A 2008 study underscored the confounding findings that often stem from Alzheimer’s disease research. Autopsies of 248 patients with Alzheimer’s disease found diabetes drugs reduced the number of lesions in their brains, though they didn’t lessen the dementia caused by the condition.
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