Alzheimer’s Disease Treatment and Treatment: A Trail of Frustrated Failures

Many are on Biogen’s drugs. If approved, it “will be the first disease modifier ever,” says George Vradenburg, chairman and co-founder of advocacy group UsAgainstAlzheimer’s. Previous drug Specially approved for Alzheimer’s disease in 2003And since then, the Alzheimer’s drug pipeline has expelled a number of unexploded ordnance.

Over the past 10 years, more than 200 prospective prospects have fallen. “Although it has been long, it has not been successful,” said Ronschneider, an Alzheimer’s disease researcher at the Keck School of Medicine at the University of Southern California, who has been studying Alzheimer’s therapeutics since the 1990s.

These failures are not the reason for trial and error. Instead, they are evidence that the disease and its causes are much more complex than researchers first recognized. “We didn’t know this [complexity]. Things seemed simpler than they really are, “says Richard Hodes, director of the National Institute on Aging (NIA).

Dementia, confusion, and personality changes are characteristic symptoms of Alzheimer’s disease. Diagnosed reliably Only by examining the brain at necropsy. The brains of people with Alzheimer’s disease show neuronal loss and the connections between them, along with characteristic plaque and protein tangles called beta-amyloid and tau.

Until relatively recently, there has been a search for drugs centered on the idea that Alzheimer’s disease develops and progresses in a specific pattern. Toxic plaques of beta amyloid aggregate between neurons in the brain. As they accumulate, tangles of tau accumulate inside neurons. These changes are associated with brain inflammation and cell death. Many drug candidates have sought to clear or disarm beta-amyloid on the basis that removing amyloid plaque stops the process and consequently stops Alzheimer’s disease itself.

Biogen’s drug is only one of many drugs designed to clear beta-amyloid, so when its trial was discontinued last spring, it initially rejected another denial of the amyloid hypothesis. It looked like.

However, in October Biogen re-analyzed data from two discontinued clinical trials of adacanumab, showing that patients receiving the highest dose of the drug had less cognitive decline in one trial than the placebo group. Interest reignited when it was discovered that it looked like. If adukanumab actually works, it is a victory in the amyloid approach.

“Biogen’s results are the most exciting results we’ve seen,” says Howard Fillit, executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation.

But others in the field are skeptical.

The benefit was seen in only one of the two trials, and the company’s analysis broke “all the rules about how to analyze and report data”. Researcher at UniversityCollege London Alzheimer Robert Howard told Journal Science.

so Commentary Schneider, published at Lancet Neurology, argues that Biogen’s method of analyzing test data means “therapeutic effects are likely to be exaggerated.”

The search for a cure for Alzheimer’s disease is plagued by failed amyloid drugs, and amyloid is beginning to look like an imperfect target. For one thing, about 40% of people in their 70s have amyloid plaques, but have no dementia, Schneider says. At the same time, some people with dementia Does not develop amyloid plaques.

Amyloid may not be a driver of the Alzheimer’s disease process, but may represent the aftermath.

“Amyloid plaques may be a sign that the brain is actually doing its job when the brain is damaged or inflamed,” said Schneider. If that is the case, it will mean that attempts to treat Alzheimer’s by eliminating amyloid are useless.

“I’m comparing amyloid plaque with a tombstone,” Schneider says. You can go to the cemetery and remove the tombstones, but people buried in the cemetery will not die.

Although the amyloid hypothesis has long dominated drug research in Alzheimer’s disease, Vradenburg says another view of Alzheimer’s disease is at the forefront. In the new approach, the approach we have used to look for Alzheimer’s disease drugs has failed because there is no single way for the disease to develop and progress. Instead, it now appears that there are various causes and pathways to the disease. And in that case, Vradenburg says, we need to treat the disease in a more personalized way.

Instead of using a single drug for Alzheimer’s disease, you may need multiple therapies that target each of the different ways it can develop and manifest. Heather Snyder, vice president of health and science at the Alzheimer’s Disease Association, said the drug pipeline is becoming more diverse, targeting other targets such as inflammation, the immune system, and metabolic processes that may be involved in Alzheimer’s disease It is said that a clinical trial has been conducted.

The hopes of finding a full-blown drug seem to be fading.

“Pee the onion—” How can I consider combination therapy? “

In 2014, drugs targeting amyloid beta accounted for the largest share of NIA-funded projects. But by 2018, Inflammation has taken over As the most common target for drug therapy. Inflammation is a characteristic of aging and appears to be involved in Alzheimer’s disease.

Funding for the disease has increased dramatically in the last decade. NIA support More than quadrupling between 2013 and 2019. Federal funding for Alzheimer’s disease research in 2020 Rose $ 2.8 billion. According to Hodes, this inflow has helped to recruit new scientists into the field, and the field has undergone a “turnaround” for more collaboration and data sharing.

Research has not yet produced drugs, but has advanced understanding of the disease in important ways that could lead to effective treatment.

At present, some of the most promising approaches to address Alzheimer’s disease are non-pharmaceuticals. The NIA supports 86 studies of potentially useful non-drug interventions, such as exercise, diet, cognitive training, and sleep. of US Pointer Survey Is a two-year clinical trial examining whether lifestyle interventions can protect older people from cognitive impairment and dementia.

Snyder says research Based on a similar one conducted in Finland and published in 2015, This shows that programs that control physical activity, cognitive simulation, Mediterranean diet, and risk factors for heart disease provide some protection against cognitive decline. Participants were at risk for dementia, but no one had it. Two years later, the risk of cognitive decline was 30% higher in the control group than in those assigned to lifestyle intervention.

Everyone wants a cure, but for now, we may need to embrace the benefits from healthy habits that we already know we should adopt.