Another big blow came to the Alzheimer’s research community late last month when pharmaceutical company Biogen and Eisai Co. announced on March 22 that they would terminate two late-stage studies of the experimental drug aducanumab. They have ceased trials after they determined it would likely fail to help patients. This announcement is the latest in a long line of failed Alzheimer’s drugs targeting the popular amyloid protein hypothesis.  

2019 Off to a Rough Start 

The year has certainly gotten off to a rocky start for Alzheimer’s researchers and pharmaceutical companies. In January, the major pharma company Roche announced it was ceasing its major human trials for a drug called crenezumab. At that point, they were deep into phase three of their trials, following years of study. The early, final trial results suggested the drug simply didn’t work to slow or reverse the damage from Alzheimer’s disease.   

Then, two months later, Bigoen is having similar results. However, the newest failure is more disappointing as aducanumab has been considered one of the most promising potential Alzheimer’s treatments in recent years.   

Origins of Aducanumab 

This drug was designed by Biogen by examining the immune cells from unusually cognitively healthy senior citizens. An antibody present in these individuals was isolated that seemed to specifically target the toxic amyloid proteins commonly associated with Alzheimer’s. The early clinical trials were promising, showing the antibody effectively and most importantly, safely, clearing amyloid plaques from Alzheimer’s patients while improving cognitive symptoms.       

Final Phase Failure in the Human Trial 

That is why there had been much optimism and anticipation in the final phase of the human trial that’s been underway for the past two years. In the announcement from Biogen this week the company states that the decision to discontinue all trials into aducanumab was based on a recommendation from an independent data monitoring committee. Early evaluation of the results thus far suggested that drug was not working and would not meet its goals. “This disappointing news confirms the complexity of treating Alzheimer’s disease and the need to further advance knowledge in neuroscience,” Biogen CEO Michel Vounatsos said. “We are incredibly grateful to all the Alzheimer’s disease patients, their families and the investigators who participated in the trials and contributed greatly to this research.” 

Amyloid Pathways Dead End 

The collapse of another Alzheimer’s drug that was targeting amyloid pathways has reignited the debate over whether scientists are pursuing the right target for Alzheimer’s treatments. There’s been a string of discontinued clinical trials that have routinely failed in reversing — or even slowing — the cognitive decline associated with Alzheimer’s. This has led researchers to question the fundamental credibility of the amyloid hypothesis. 

“Something is wrong with the way we’re thinking about Alzheimer’s and amyloid, folks, something is wrong,” researcher Derek Lowe, a longtime sceptic of the amyloid hypothesis, wrote on the Science Translational Medicine blog. “It’s been wrong for a long time and that’s been clear for a long time. Do something else.” 

Need to Shift Focus 

Some neuroscientists suggest the problem may not be in targeting amyloid itself, but instead could be more related to the disease stage many of these trials are focused on. It’s been hypothesized that once amyloid has accumulated and caused neurological damage, it’s simply too late to try these kinds of anti-amyloid treatments 

In reaction to the news, John Hardy, Professor of Neuroscience at University College of London, shared in the Science Media Centre blog, “What this failure appears to teach us is that removing amyloid from the brain after it has deposited does little good. This is the simplest explanation of the trial failure. For amyloid therapies to work, we need to identify people before they start to lose nerve cells.” 

Also extremely interesting are some of the alternative theories that there may be no silver bullet medication as a “cure.” Instead, that Alzheimer’s arises as a result of the human body’s response to several stimuli, and that a more thoughtful, combined approach will ultimately provide the solution. 

Undeniably, failure in the late-stage of testing is a setback, but there are quite a few researchers who’ve been inspired by the recent amyloid failures, simply because it has pushed them to pursue different causes of Alzheimer’s disease. News Atlas reports that some of the causes that are being pursued include abnormal levels of brain iron, the herpes virus, poor sleep habits and gum disease. While we still might be far from finding an effective treatment to Alzheimer’s disease, optimists would point out that this latest failure is not the end, but rather a challenge to redirect and pursue the real cause of this devastating disease. 

If you would like to read more about research to prevent Alzheimer’s disease, read our blog “Texas Research: Alzheimer’s Disease Vaccine in the Works.

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