A new Alzheimer’s disease drug may be able to clear away goopy piles of toxic proteins in patients' brains—hallmarks of the progressive disorder. The drug is an antibody directed at the proteins themselves, and the promising results come from a small, phase I safety trial.

To date, no other drug has shown this much brain-clearing power. If the results hold up in larger trials, the drug has the potential to prevent or even reverse the progression of the disease. But researchers caution that excitement should be tempered; it's far too early to decipher the drug’s true potential. Similar antibody-based drugs have given promising results in early trials but went on to fail spectacularly in larger studies—in some cases even causing death.

“I am cautiously optimistic about this treatment, but trying not to get too excited,” Tara Spires-Jones, interim director of the Centre for Cognitive and Neural Systems at the University of Edinburgh, said in a media statement. “This was a small phase I study with 20-30 people in each treatment group. We will have to wait and see whether the promising results reported here are repeated in the larger phase III trials of this drug that are currently underway worldwide.”

The researchers behind the trial, led by scientists at pharmaceutical companies Biogen and Neurimmune, also reported that some of the patients receiving the drug appeared to have slower cognitive declines than those in the placebo group. However, that data is inconclusive due to the small size of the trial. “Clinical assessments were exploratory as the study was not powered to detect clinical change,” they noted in the study, published Wednesday in Nature.

The trial started with 165 patients total and involved administering an antibody that targets the amyloid-beta protein, misfolded wads of which amass in the brains of Alzheimer's patients. Many researchers argue that these protein blobs are the cause of Alzheimer’s symptoms, but we don't know enough to say for sure—the tangles themselves could also be a symptom. Amyloid-beta normally accumulates in clumps by old age but to a much greater extent in those suffering from the progressive disorder.

Researchers have been working for decades to try to train the immune system to go after the protein deposits. But past trials, even those with promising preliminary results, have failed to yield a safe and effective drug.

One of the many complications of sweeping away the protein plaques is that amyloid-beta tends to accumulate in blood vessels in the brain. Breaking up the clumps therefore has the potential to rupture the vessels, leading to hemorrhaging. Recruiting the immune system to do the cleanup also risks the potential of an overzealous response, leading to dangerous brain inflammation.

In past studies, researchers noted these adverse events can show up during trials as smudge-like abnormalities on brain images, which are often used to track the progress of plaque clearance. Those image smudges, called amyloid related imaging abnormalities (ARIAs), can signal problems like fluid buildup and hemorrhaging, but they could also be nothing to worry about.

In the current study, ARIAs were the top side-effect reported in those receiving the treatment. Of the 165 patients,125 were broken into four groups receiving a different dose of the antibody drug, called aducanumab, given intravenously once a month. The remaining 40 received placebo. By the end of the 54-week study, 40 patients dropped out, leaving 125. The top reason was adverse side-effects.

The researchers noted that the higher the dose of aducanumab, the more plaque clearance they saw—a positive sign that the drug worked. But they also reported that the higher the dose, the more ARIAs showed up. Of the 32 people receiving the highest drug dose, 15 had some type of ARIA and 10 patients in the group dropped out because of an adverse event.

“Although encouraging, the main problem encountered with this study was the relatively large number of participants who dropped out because of side-effects involving changes in blood vessels that supply the brain,” David Allsop, a neuroscientist at the University of Lancaster said in a media statement. “This problem has been encountered previously and will have to be overcome if this type of therapy is to find widespread clinical use. Nevertheless, these findings could be a 'game changer' if the effects on memory decline can be confirmed in more extensive follow-on studies.”

Two larger phase III trials, which test the efficacy of drugs, are now in progress and are scheduled to run into 2020.

Nature, 2016. DOI: 10.1038/nature19323 (About DOIs).