An experimental drug dramatically reduced the toxic plaques found in the brains of patients with Alzheimer's disease, a team reports in the journal Nature.
Results from a small number of patients who received a high dose of the drug, called aducanumab, hint that it may also be able to slow the loss of memory and thinking.
"If that hint of a clinical benefit is confirmed, it would be a game changer in the fight against Alzheimer's disease," says Dr. Eric Reiman, executive director of the Banner Alzheimer's Institute in Phoenix. Reiman wrote a commentary that accompanies the study in Nature.
But it will take much larger studies to show for sure whether aducanumab really does slow down Alzheimer's disease, Reiman says.
Officials of Biogen, which is developing the drug, were also cautious about interpreting the results of the study, which included 165 patients in the early stages of Alzheimer's disease.
"We think we have something important here," says Dr. Alfred Sandrock, chief medical officer for Biogen. "We hope we're right because if it's true it would benefit millions of patients. But we don't know we're right yet."
The results are encouraging for pharmaceutical companies that have spent billions of dollars on efforts to come up with the first drug to treat the underlying cause of Alzheimer's. Those efforts have failed to produce a single approved drug so far.
But last summer, Biogen began presenting its results with aducanumab at scientific meetings, including the Alzheimer's Association International Conference in July. These early reports suggested the drug had a remarkable ability to remove plaques in the brain.
"It was surprising, encouraging and thought-provoking to see such a striking reduction of existing plaques," Reiman says.
The publication in Nature on Wednesday provides details about those early reports.
Biogen has already begun two much larger studies of aducanumab. They will include a total of 2,700 patients, and results are still several years off.
But there are reasons to think aducanumab may succeed where other drugs have failed.
One is that the drug appears to ignore benign forms of amyloid protein while attacking the toxic forms thought to damage brain cells. Another is that aducanumab seems to enhance the ability of existing immune cells in the brain to devour toxins, including amyloid.
But there's a downside. The process of removing plaque sometimes causes fluid to build up in the brain. In rare cases, it can also cause bleeding. These side effects are known as amyloid-related imaging abnormalities, or ARIA.
"We were actually anticipating that we would see it," Sandrock says. And the researchers did. Twenty patients dropped out of the trial because of adverse effects.
If aducanumab works in larger studies, it could help settle a long-running debate about whether amyloid is really the root cause of Alzheimer's. This idea is known as the amyloid hypothesis.
And large studies showing that removing amyloid can preserve memory and thinking "would go a long way toward validating the amyloid hypothesis," Sandrock says.
Results like those could also lead to the first approved drug to treat the underlying cause of Alzheimer's rather than just the symptoms.
ARI SHAPIRO, HOST:
Here's a glimmer of hope for people in the early stages of Alzheimer's disease. A new study shows that an experimental drug can scrub away plaques in the brain that are a hallmark of the disease. But as NPR's Jon Hamilton reports, it is still not clear whether the drug can improve memory and thinking.
JON HAMILTON, BYLINE: Pharmaceutical companies have come up with a lot of drugs meant to fight Alzheimer's. So far they've all failed. But last summer, scientists began hearing about a drug called aducanumab. Early reports suggested it had a remarkable ability to remove the toxic amyloid plaques that build up in the brains of people with Alzheimer's. Dr. Eric Reiman is executive director of the Banner Alzheimer's Institute in Phoenix.
ERIC REIMAN: It was surprising, encouraging and thought-provoking to see such a striking reduction of existing plaques.
HAMILTON: Now those findings have been published in the journal Nature. A study of 165 people in the early stages of Alzheimer's confirms that aducanumab is a potent plaque buster, and Reiman, who wrote an editorial accompanying the study, says that's not all.
REIMAN: There was a hint that the reduction in amyloid plaques may be associated with a slowing in memory and thinking problems.
HAMILTON: Reiman says people who took the highest dose of the drug had very little cognitive decline.
REIMAN: If that hint of a clinical benefit is confirmed, it would be a game changer in the fight against Alzheimer's disease.
HAMILTON: Even Biogen, the company that's developing aducanumab, is being cautious. Al Sandrock is the company's chief medical officer and an author of the new study.
ALFRED SANDROCK: We think we have something important here. We hope we're right because if it's true, it would benefit millions of patients. But we don't know where right yet. We're going to have to do a couple of large trials to confirm what we think we see.
HAMILTON: Those trials will include a total of 2,700 patients. Researchers began enrolling those patients last year, but results are still several years off. Sandrock says there are several reasons to think aducanumab will succeed where other drugs have failed.
SANDROCK: First of all, it seems to be more specific for the toxic forms of amyloid.
HAMILTON: The drug appears to target the amyloid cluster suspected of damaging brain cells while ignoring benign forms of the protein. Also, the drug appears to ramp up immune cells in the brain that devour toxins, including amyloid.
But there's a downside. The process of removing plaque sometimes causes fluid to build up in the brain. In rare cases it can also cause bleeding. Sandrock says these side effects are known as ARIA.
SANDROCK: We were actually anticipating that we would see it. We actually did frequent MRI scans to actually look for the ARIA. We did see it.
HAMILTON: But the problems were usually mild, and most patients were able to continue taking the drug. If aducanumab works in larger studies, it could help settle a long-running debate about whether amyloid is really the root cause of Alzheimer's. This idea is known as the amyloid hypothesis, and Sandrock says he's a believer.
SANDROCK: We're very hopeful that we'll actually see a cognitive benefit. And if we do, I believe it goes a long way toward validating the amyloid hypothesis.
HAMILTON: And it could lead to the first drug that would treat the underlying cause of Alzheimer's rather than just the symptoms. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.