At OHSU, researchers will test promising Alzheimer’s drug and find out why

Drugs to treat Alzheimer’s disease have been in development for decades. However, almost all clinical trials have been disappointing.

One theory is that we treat people too late and not long enough.

Oregon Health and Science University is now Participation It is one of the first studies to attempt early intervention in healthy older adults aged 55 to 80 who are at risk of developing Alzheimer’s disease as they age.

An international clinical trial called AHEADResearchfunded by the National Institutes of Health and pharmaceutical company Eisai.

Clinical trials are ongoing, but scientists focused on Alzheimer’s disease research have come up with a leading theory about the cause of Alzheimer’s disease, amyloid hypothesis, may error.

The AHEAD study is both a test of a single promising drug and an effort to uncover more evidence about how Alzheimer’s disease begins.

The main focus of this study is a drug called lecanemab. It just received accelerated approval from the FDA for use in patients with early or mild Alzheimer’s disease.and it is first medicine It’s backed by solid data showing it may slow the progression of Alzheimer’s disease.

These are called anti-amyloid antibodies. Some scientists believe that lecanemab and other anti-amyloid drugs in development are more effective if given before typical Alzheimer’s symptoms such as memory loss appear.

Barbara Klausman is exactly who AHEAD researchers are looking to join their research. She Klausman lives in Vancouver. she is 76 years old. But last fall she looked much younger one day in November in her stylish dark green tennis shoes matched with jeans and a sweater.

“I look forward to waking up every day because there’s always something to do,” Kraussman said that day as he sat in OHSU’s small clinic, preparing for an injection of what he believed to be lecanemab. She also knew that it might just be saline, a placebo.

She has a very personal reason for volunteering for these infusions.

“It was 1989 and my brother was in the military in Europe as a dentist. I wrote him a letter, ‘There’s something wrong with my mother,'” Klausman said.

Klausmann watched Alzheimer’s disease take over his mother’s heart. Clausmann did everything he could for his mother. If she had an episode of excitement in the middle of the night, her dad would call.

“Then I picked her up and went for coffee so she forgot she was upset and I took her home,” Kraussman said. I was.

In most cases, the disease progresses slowly. When neurons in the brain die, patients experience memory loss, then dementia, and eventually death. Alzheimer’s disease is one of the leading causes of death for people over the age of 65.

Krausmann’s mother passed away in 2003. But she felt that she had lost her mother many years ago.

“It’s just hard to see someone you love going through that,” Kraussman said last fall, nearly 20 years after his mother’s death. It wasn’t her, and yet she needed to be loved.”

Klausman’s aunt also had Alzheimer’s disease, and presumably so did her grandfather. That question led her to a team of researchers at OHSU who were involved in the AHEAD study.

“With Alzheimer’s disease, like any other disease, if you can catch it early and treat it early, you’ll most likely have a better chance of fighting it,” said a geriatric neurologist, OHSU Study Lead.

Pierce and her team are using brain imaging to look for amyloid plaques and tau tangles, two distinct markers of the disease.

We’ll talk about tau later. First, amyloid.

No one is quite sure what causes Alzheimer’s disease, but scientists have long suspected that a fragment of a protein called amyloid beta forms abnormal plaques in the brains of patients. . There is also some genetic evidence pointing to this particular protein from families with early-onset familial Alzheimer’s disease and people with Down’s syndrome.

Anti-amyloid antibodies such as lecanemab are can clear plaque from the patient’s brain. However, in clinical trials, these drugs did not slow, if at all, the progression of dementia in patients.

That’s why we’re trying to dose people years before plaque is just starting to form.

“We know these plaques are found in people with Alzheimer’s disease,” Pierce said. “But we think it forms years before the symptoms of Alzheimer’s appear.”

Today, Klausman has no symptoms of Alzheimer’s disease or unusual memory loss that most GPs suspect. However, her brain scan confirmed that she had already developed amyloid plaques in her brain, which could put her at risk for the disease.

An important caveat here: not everyone with plaques will develop Alzheimer’s disease. It’s just a risk factor.

As a study participant, Klausman receives intravenous fluids at OHSU at least once a month.

“It’s never too bad. It’s not that bad,” she reassured the therapist who set an IV in her arm last October.

“That’s good,” he quipped. “When you show up with a needle, you don’t want people to hate you.”

This approach—needs to be administered via IV, very serious Side effects—There are many things to ask study participants.

Klausman participated in this trial a year ago. She has her 3 year implant to go.

She also regularly has two types of brain scans. And for scientists to see if taking lecanemab can prevent memory loss, Kraussman will have to undergo a number of cognitive tests.

“It’s not my favorite thing to do,” she said of the test. “I like to pass tests.”

And to protect the reliability of the research data, she doesn’t know what the test found. That means half of the participants were taking a placebo instead of the real drug. To avoid bias, neither Klausmann nor her researchers know which group she belongs to. She won’t know until the research is over.

“You know the options for what’s revealed, one could be a real downer,” she said.

Since this is a work in progress science, there is no guarantee that it will work even if Krausman is taking lecanemab.

One major reason for skepticism is that the amyloid plaques that lecanamab clears from the brain may not be the underlying cause of Alzheimer’s disease. Although they have been the focus of most research, some scientists believe plaque is a red herring or even part of the body’s efforts to protect brain cells from damage. Basically, plaque could be a bandage rather than a wound.

So some scientists believe the real culprit is something else. Perhaps it’s tau. This is another protein fragment that is characteristic of this disease. In the brains of Alzheimer’s disease patients, tau appears as tangles within neurons. Until relatively recently, they were difficult to see on brain imaging scans of living patients.

For a long time, the prevailing theory was that amyloid build-up somehow caused harmful tau tangles. Yes, said Pierce.

The question now is, “Do amyloid plaques really accumulate before tau tangles occur? Indeed, it is surprisingly difficult to determine,” she said. “It requires considerable long-term research.”

The AHEAD study was one of the first to obtain images of both amyloid and tau in brain scans of over 1000 elderly people.

Pierce and the rest of the team will be able to compare these images to how participants are performing on cognitive tests. And it may help unlock the central mystery of how Alzheimer’s disease begins.

For Klausman, the reason for joining is very clear. She can help find a cure for the illness that struck her mother. She also has two daughters of her own, so when I think about her family history and risk of illness, I think of her daughters as well.

I hope a cure will be available in her lifetime, but she doesn’t expect it.

“By doing research like this, by the time they have to worry about 20 years from now, they’re either no longer worried or there’s a cure,” Klausman said of her daughters. “Yes, I am doing this for them and future generations.”