New Alzheimer's drug trial gives researchers optimism

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New Alzheimer's drug trial gives researchers optimism
Karen Weintraub, Special to USA TODAY Published 2:27 p.m. ET July 20, 2018


No effective treatment for Alzheimer's is yet in sight, but better diagnostics, deeper scientific understanding and an encouraging drug trial are all leading to a positive mood, as the largest Alzheimer’s research conference of the year begins Sunday in Chicago.
“There have been plenty of disappointments and sadly I’m an expert in those disappointments,” said Stephen Salloway, director of the Memory and Aging Program at Butler Hospital in Rhode Island and a professor of neurology at the Alpert Medical School of Brown University. “ (But) I’m quite bullish and think we’re making significant progress.”
Much of the recent optimism surrounds a drug trial that will report out more details at the Alzheimer's Association International Conference.
In that small trial, a drug seems to have removed a protein called amyloid, which is the hallmark of Alzheimer’s. All previous trials attacking amyloid, including some costing hundreds of millions of dollars, have failed in patients. The new study suggests it’s because they were given too little, too late.

“You’re going to have to move early and be very aggressive,” said Reisa Sperling, who directs the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital in Boston.
Eighteen months after they began taking the experimental drug – called BAN2401 –patients who received the highest dose saw a dramatic drop in the amyloid in their brains as well as signs that disease progression had slowed, according to Biogen, which is developing the drug along with Japanese company Essai. Detailed results and more recent findings are expected to be presented at the conference.
“I’ve seen the data and I find them very encouraging for a change,” said Sperling, a professor of neurology at Harvard Medical School.
Exactly how early the treatments should be started remains unclear.
Other trials, including the recently announced Alzheimer’s Prevention Initiative Generation Program, a collaboration between drug companies Novartis and Amgen and the nonprofit Banner Alzheimer’s Institute, are trying similar drugs earlier in the disease, before people have noticeable symptoms.

Such early approaches are largely possible because of a diagnostic test approved in 2012 that can confirm amyloid in the brain before the person suffers obvious memory loss. The PET scan diagnostic is not available to most patients, because it’s not routinely covered by Medicare, but has been used in clinical trials to make sure that only people who have amyloid in their brains are given the anti-amyloid drugs. Many earlier anti-amyloid drug trials turned out to have included people who had dementia, but not Alzheimer’s, so the drug would never have worked on them.
About 5.7 million Americans have Alzheimer’s disease, which is the most common form of dementia. That number is expected to climb to nearly 14 million by 2050, as the population ages.
Although anti-amyloid drugs are still considered the most promising to treat early forms of Alzheimer’s, researchers are also developing candidate drugs that act on other aspects of the disease. An experimental diagnostic PET scan can visualize the build-up of another protein that’s characteristic of Alzheimer’s, called tau.

Trials are underway to see if drugs that remove tau will benefit people with Alzheimer’s. Sperling said she’s excited about the potential of this work, but notes that researchers must still figure out how much of these drugs to give, which form of tau to go after, and what stage of the disease to treat with these drugs. “We have years of work ahead,” she said.
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A combination of treatments – maybe an anti-amyloid and an anti-tau drug – might prove to be the best approach, particularly as the disease advances, Sperling said.
People at later stages of the disease have very little to help them right now, and not much on the near-term horizon, Salloway admitted.
“We haven’t had a new treatment for symptomatic Alzheimer’s for more than 13 years,” he said. “I’m not seeing anything at the moment.”
He and several other researchers pointed to a drug recently approved for psychosis among Parkinson’s disease patients that might also prove useful in Alzheimer’s.
Pierre Tariot, a geriatric psychiatrist and director of Banner Alzheimer's Institute, said he’s hopeful some new therapies will come along in the next 3-5 years that will address the emotional and psychological aspects of the disease, and others that will allow people to hold onto their intellectual function longer.

Patients and their loved ones would be grateful for any improvements that allow them to participate in family events or even something as simple as making their own breakfast. “They’re not looking for miracles,” he said.
Research suggests lifestyle changes may help prevent as many as one-third of Alzheimer’s cases. Studies show that people who exercise more in mid-life may be less likely to develop the disease decades later.
Maintaining social engagement with age is also considered important, as is a healthy diet and good sleep. Sperling also suggests ballroom dancing lessons or group activities.
Even when there are effective drug treatments, lifestyle changes will still be important, said Ronald Petersen, who directs the Mayo Clinic Alzheimer's Disease Research Center in Rochester, Minnesota. Petersen said the best hope for drugs long-term will be to delay the onset and slow the progression of Alzheimer’s – not avoid it completely. “I think that’s more realistic,” he said.
Salloway said people can help themselves and others by volunteering for Alzheimer’s research studies. Salloway runs “cheek swabbing parties” to help identify people with the APOE4 gene, which raises Alzheimer’s risk with age. Many Alzheimer’s studies look specifically for people with one or more copies of this gene because of their elevated risk.
Still other drugs at earlier stages of development are trying to address brain inflammation, vascular problems, misshapen proteins and the microbes in the gut, any of which might alone or in combination trigger or exacerbate Alzheimer’s.

There are even drugs being tested that might work on the fundamental biology of aging, delaying diseases, including heart disease, cancer and Alzheimer’s.
It’s this flood of different approaches that gives hope to Eliezer Masliah, director of the division of neuroscience at the National Institute on Aging, which supports more than 170 different drug trials and research studies.
Howard Fillit, founding executive director and chief science officer of The Alzheimer's Drug Discovery Foundation, said he’s never been more upbeat in the nearly 40 years he’s worked in the field.
Federal research funding has reached $1.9 billion this year, although Fillit said more is still needed. Last week, a group of philanthropists including Bill Gates and Fillit’s organization announced the creation of a $30 million accelerator fund to support the development of new Alzheimer’s diagnostics. The hope will be to develop a simple blood test that could diagnose Alzheimer’s and track both the disease and any treatment, Fillit said.
“We’re like 60 years behind cancer and heart disease and diabetes, but we’ve caught up really rapidly,” he said, saying that Alzheimer’s research didn’t begin to make real progress until the mid-1980s, and that it usually takes at least 30 years for drugs to be developed out of basic scientific research.