Alzheimer's researchers are excited.
Aducanumab, an investigational drug being developed by Biogen, is at the center of it all. In a small trial, the drug appeared to trigger a major reduction in what's known as amyloid; a.k.a. plaque in the brain that experts see as a key player in the development of dementia.
The kicker? For patients in the early stages of Alzheimer's disease, the drug also seems to have put the brakes on cognitive decline.
"In very early cases, they were able to dramatically hit amyloid, and along with that, they got some signals that suggested they were also improving cognition. This is the first amyloid-targeted therapy to do this," Rudolph Tanzi, Ph.D., a renowned Alzheimer's researcher and Professor of Neurology at Harvard Medical School, tells The Current.
The study's implications, which were expounded upon in a 2016 report published in Nature, have experts like Tanzi buzzing. While we're still far from curing the disease, Aducanumab looks like a major step in the right direction.
Understanding the magnitude of these implications requires taking a closer look at what we know about Alzheimer's disease. According to Tanzi, most people experience a natural buildup of amyloid in the brain as they age. This, in turn, leads to what are called neurofibrillary tangles that trigger inflammation. This last bit is key as this is what kills neurons and ultimately causes memory loss and other telltale signs of dementia.
"Plaque and tangles push you up the hill, and you can live there for a long time, but it's inflammation that throws you off the top," says Tanzi.
Before Aducanumab came on the scene, amyloid-targeted clinical trials had been laser focused on patients who'd already fallen down that hill. As Tanzi puts it, it's like trying to put out a forest fire by blowing out the match that started it. Aducanumab is novel in that it's the only antibody to show promise among patients who have amyloid in the brain and are in the earliest stages of the disease. While other therapies have been successful at clearing out plaque, Aducanumab is the first to apparently press pause on cognitive deficiencies.
The bottom line
"That amazed us because the bottom line is with Aducanumab, we can actually see some benefit on cognition," adds Tanzi.
But there's still a lot we don't know. For starters, this was a small trial, so it's unclear how it'll hold up in a larger study. Another key piece of the puzzle is that the dose that appears to be the most effective is also the highest dose. The caveat here is that this high dose was also associated with the most adverse events; some patients experienced swelling in the brain or even mild hemorrhage.
"In the first Aducanumab trial, these adverse events occurred in people who carry a specific risk allele that is present in about 60 percent of patients," says Tanzi. "So hypothetically, these people may be limited to a lower dose, but we'll have to see how it all plays out."
The good news is that these side effects were reversible, but it makes Tanzi wonder what this might mean for Aducanumab's potential as a long-term drug. Just as we might take statins for decades to keep our cholesterol under control, would it be possible to develop a maintenance drug to keep amyloid in check over the long haul? Similarly, could a more aggressive approach like Aducanumab sweep in and safely clear major chunks of amyloid from the brain? At this point, we just don't know.
That said, Aducanumab represents a major breakthrough when it comes to unraveling the mysteries of Alzheimer's disease. Hitting amyloid early—before neuroinflammation pushes you down the hill—appears to be a critical component. In Tanzi's vision, the future of Alzheimer's eradication lies in prevention. Just as colonoscopy is commonplace once you turn 50, what if PET scans to identify amyloid become a regular preventative measure? If Biogen indeed develops an amyloid-eating medication that can slow cognitive decline (or, better yet, prevent it all together), it could, at least theoretically, signal the beginning of the end of Alzheimer's disease.
Of course, the operative word here is "theoretically."
"There are still question marks, but I think it's fair to say that Aducanumab is really the greatest hope out there for a trial," says Tanzi. "That said, it's still in my mind 50/50 as to whether we'll see cognitive benefits."
In the meantime, Biogen released its most recent data at the end of August, after which shares went up 2.5 percent, according to a Nasdaq report; good news for those committed to investing with intention.
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