Now more than ever, Alzheimer's disease poses an enormous burden. The neurodegenerative disease afflicts more than five million Americans, robbing them of their memories and placing strain and heartache on their loved ones. This toll costs the U.S. economy hundreds of billions of dollars each year.
But a new study of mice published in the Journal of Experimental Medicine suggests that by shutting off just one protein, future medications could potentially break up the sticky plaques associated with Alzheimer's.
The protein in question, BACE1, plays a fundamental role in neural development. It also makes the raw materials that form beta-amyloid plaques, the sticky gloms of protein found in the brains of Alzheimer's patients. Some researchers suspect that as beta-amyloid plaques build up, they prevent nerves from talking to each other, causing the disease's symptoms.
BRAIN 101 The brain constitutes only about 2 percent of the human body, yet it is responsible for all of the body's functions. Learn about the parts of the human brain, as well as its unique defenses, like the blood brain barrier.
For years, researchers have tried making drugs that shut down BACE1. To model the effects of these future drugs, researchers at the Cleveland Clinic Lerner Research Institute bred a line of mice that developed Alzheimer's-like plaques in their brains. In addition, the researchers could turn off the specially bred mice's BACE1 genes at will, thanks to a system called the Cre-lox process.
The team then tracked cohorts of 12 of the specially bred mice, to see how deactivating BACE1 changed their brains over time. At the 75-day mark, these mice formed beta-amyloid plaques, but the plaques vanished as the mice continued aging. By the time the mice were 10 months old, researchers couldn't detect plaques in the mice's brains.
Cognitive tests showed that as the mice lost plaques, their learning and memory improved, though not back to levels seen in Alzheimer's-free mice that still had BACE1.
"To our knowledge, this is the first observation of such a dramatic reversal of amyloid deposition in any study of Alzheimer's disease mouse models," said coauthor Riqiang Yan, the co-discoverer of BACE1, in a statement.
LONG WAY TO GO
While the study's results are impressive, we must be careful about what they do and don't mean.
For one, this study was done with mice, not humans, and this genetic experiment mimicked how medicines would target BACE1. It did not test a medication itself.
What's more, the oldest mice in this study were only 10 months old, roughly equivalent to middle-aged humans. Perhaps older mice will not heal as effectively; in the study, the researchers write that even older mice should be tested.
Nevertheless, the finding likely comes as welcome news to drug developers seeking to target BACE1. Drugs aiming to shut down the protein are in clinical trials, but recent efforts have ended with disappointment.
For instance, consider verubecestat, a BACE1 inhibitor under development by Merck Pharmaceuticals. Early clinical trials showed promise, but on February 13, Merck ended a trial for the drug among early-stage Alzheimer's patients, citing its ineffectiveness.
In general, new drugs take years of work. PhRMA, the major trade association for drug companies, estimates that developing a given medicine takes at least a decade. A 2016 study in the Journal of Health Economics found that the R&D that goes into a new medicine costs about $2.6 billion, on average.
Lead image: Brain 101 still