Alzheimer’s researchers see first promising therapies in decades




SACRAMENTO, Calif. — For decades, Alzheimer’s disease has been silently ravaging brains, stealing memories and shortening the lives of millions of Americans. Now, researchers say they may be on the brink of tantalizing treatment breakthroughs that could for the first time at least slow the disease’s deadly progression.

It could help patients such as David Johnson, a 59-year-old former truck driver in Sacramento, who wasn’t surprised when he was diagnosed with early-onset Alzheimer’s in 2012. The debilitating disease had already taken his father, six aunts and uncles, and a cousin.

Four years ago, “I resigned myself to dying. I knew I had three to five years left,” said Mr. Johnson, a trim, goateed grandfather.

Instead, he was enrolled in a clinical trial at Sacramento’s Sutter Neuroscience Institute that Mr. Johnson believes has slowed, if not halted, the disease.

Four years into the five-year clinical trial, it’s still too soon for Sutter Health doctors to confirm how well Mr. Johnson’s treatment, involving infusions of special antibodies, is working. So far, his brain scans have showed the disease has not progressed.

Mr. Johnson’s treatment is one of hundreds of clinical trials underway nationwide focused on Alzheimer’s and dementia. Amyloid, the sticky protein that attaches to brain cells and causes Alzheimer’s, is at the forefront of new therapies. Although none of the clinical therapies are yet FDA-approved, some are in the final phases with promising results, say researchers.

If so, it could mean the arrival of disease-disrupting treatments that patients, caregivers and researchers have been eagerly anticipating for decades.

“We’re entering a new era where we are very close to having the first proven disease-modifying therapy. It’s taken an awful lot of work for the last decade, but we think it’s slowing down the progression of the disease,” said Dr. John Olichney, neurology professor and director of clinical trials for the University of California, Davis Alzheimer’s Disease Center.

More than 5 million Americans are living with Alzheimer’s, a progressive form of dementia that destroys brain cells. It’s the sixth-leading cause of death among U.S. adults.

As the median U.S. age rises over the next decades, the number of people with Alzheimer’s is estimated to grow to 13.8 million by 2050 in the absence of new treatments.

“It’s a scary diagnosis,” said Dr. Shawn Kile, a neurologist who oversees Sutter Health’s six Alzheimer’s research studies, including the trial involving Mr. Johnson. “It’s fairly common, so people often have had a loved one or close friend go through Alzheimer’s and have seen the direct effect. [Patients] lose their memory and lose who they are. It leads to continued deterioration and eventually death.”

Mr. Johnson’s trial treatment involved a series of five infusions of a blood product called intravenous immunoglobulin, or IVIG, whose antibodies help clear or remove amyloid, the sticky, abnormal brain protein found in Alzheimer’s patients.

Currently prescribed drugs such as Aricept and Rivastigmine, which help certain brain transmissions involved with memory, are able to temporarily rewind the clock in dementia patients, boosting their short-term memory for a time. But they do nothing to slow down the disease’s relentless advancement in the brain.

Now, new clinical trials in Sacramento and elsewhere may be slowing the rate of decline in Alzheimer’s patients.

An estimated 5,000 researchers here and across the country are conducting trials into Alzheimer’s treatments. UC Davis, for instance, is conducting several clinical trials, including looking at the impact of Vitamin D on cognitive function and examining ethnic disparities in Alzheimer’s treatments.

“Although these [new therapies] may not be a home run and don’t cure the disease, if we slow it down by 25 to 33 percent, that’d be a whole extra year of function. That would be better than all the current therapies,” Dr. Olichney said.

In the last five years, U.S. spending on Alzheimer’s research has roughly doubled, climbing to an estimated $991 million in 2016, according to the National Institutes of Health.

But that’s still not nearly enough, say advocates and researchers, who estimate it will take $2 billion over 10 years to reach U.S. goals outlined in the National Alzheimer’s Project Act, a law designed to put more muscle into defeating the disease. Those goals include earlier detection, better treatments to prevent or delay the disease and a reduction in long-term care costs.

Compared with other diseases, Alzheimer’s “gets a lot less funding than cancer, heart disease, AIDS,” said Michelle Johnston, regional director of the Greater Sacramento office of the national Alzheimer’s Association. “Unlike other diseases, people with Alzheimer’s cannot advocate for themselves.”

Because it’s age-related, the vast majority of Alzheimer’s patients are diagnosed at age 65 or older.

“If we could find a way to slow the progression by five years, we’d cut the number of cases and the cost almost in half,” she said, citing research conducted for the national Alzheimer’s project.

Unlike with other diseases, Ms. Johnston said, Alzheimer’s patients often battle a stigma that makes some patients reluctant to discuss their illness. But that’s changing as celebrities, such as country singer Glen Campbell and longtime women’s college basketball coach Pat Summitt, have spoken up, she said.

Mr. Campbell, diagnosed in 2011, went on a farewell tour a few years ago and now lives in a Florida care facility, having lost his ability to speak, according to news reports quoting his wife. Ms. Summitt, an Olympic medalist who broke NCAA records as a women’s college coach, died in June at age 64, five years after being diagnosed with early-onset Alzheimer’s.

During the past three decades, “remarkable progress” has been made in understanding the neurobiology of chronic brain diseases such as Alzheimer’s, notes a 2012 report by a national group of Alzheimer’s researchers, part of the U.S. plan to defeat the disease. “Research on the aging brain and dementia has moved from relative obscurity to the forefront of neuroscience,” the report read.

One research effort identifies the disease earlier, even before symptoms appear — partly motivated by previous research showing some treatments were more effective in the disease’s early stages.

“We used to say you couldn’t accurately diagnose Alzheimer’s until an autopsy, not with 100 percent certainty,” said Dr. Kile, who heads a clinical trial on the effectiveness of PET scans for diagnosis. “Now, we can diagnose it 10 to 15 years before symptoms begin to show. It’s a breakthrough.”

Sutter is accepting 20 to 50 patients, age 65 and older, who will undergo a PET scan to check for any amyloid plaque deposits in their brains — part of a national study involving nearly 18,500 Medicare beneficiaries.

The scans are considered a more accurate, but often more expensive, diagnostic tool, compared with spinal fluid or genetic tests. In the clinical trial, the scans, which can cost as much as $4,000, will be covered by Medicare.

With an earlier diagnosis, patients could become eligible for earlier treatments such as anti-amyloid therapies.

Patients will be tracked over 12 months for the number of diagnostic tests, emergency room visits and hospital admissions compared with a non-PET scan group.

Sutter’s Dr. Kile said the goal is to continue diagnosing the disease “earlier and more accurately” so that patients can get into the right treatment plan and clinical trials, where possible.

Finding those trials isn’t always easy, however.

The national Alzheimer’s Association has a free matchup service, where an individual’s online questionnaire is matched with a database of hundreds of clinical trials worldwide. Participants can include patients, healthy seniors and Alzheimer’s caregivers. The trials range from brain imaging to blood work to behavioral modification, either online or in person.

Although all clinical trials have risks, they offer hope for some patients.

At the time of Mr. Johnson’s diagnosis, “he was going downhill so fast,” said Joni, his wife of 35 years. The longtime Teamsters trucker was starting to forget how to get through an intersection or make a simple left-hand turn into a shopping center. He also had trouble making change with cash.

Today, he’s not 100 percent better, but everything has improved. Although forced to give up his commercial driver’s license, he can still drive a car. He can’t follow a novel, but he reads a daily newspaper. He no longer balances the family checkbook, but his recall of numbers and short-term memories is clearer. And he easily enjoys socializing with family and golfing buddies, some of whom didn’t expect him to make it beyond the first year after his diagnosis.

For Mr. Johnson, living with Alzheimer’s at this early stage is still manageable. At 7 a.m. every Saturday, the grandfather of six is a volunteer greeter at the Cordova Golf Course, welcoming golfers and making sure they’re stepping onto the first tee at the right time.

Compared to how quickly the disease accelerated in his father and other now-deceased family members, Mr. Johnson said he feels grateful.

Getting into a clinical trial, he said, “was the luck of the draw. I got a lucky card.”





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