Scientists reversed Alzheimer’s disease in mice. Can they do this in humans?

Scientists reported Tuesday that they had the opposite Alzheimer’s disease In mice, a breakthrough that offers hope for a potential treatment for the devastating form of dementia in humans.

In a paper published Tuesday in Signal transduction and targeted therapyIn this article, a team of researchers describes how, by harnessing the brain’s garbage disposal system, they were able to repair the brain and reverse the progression of disease in animals.

Specifically, they used nanotechnology to target and restore the brain’s “vascular gatekeeper,” the blood-brain barrier, which protects the brain from toxins and streamlines blood flow in and out of the brain.

Maintenance work

The new method came from studying how the buildup of “waste” proteins such as amyloid beta (Aβ) impairs nerve cell function. Sometimes, clever solutions to complex problems come from going back to basics.

The blood-brain barrier normally filters unwanted substances from the brain, but in people with Alzheimer’s disease, the barrier becomes blocked or fails to respond properly to intruders.

“We think it works like a cascade: when toxic species like Aβ accumulate, the disease progresses,” Giuseppe Battaglia, senior author on the study and a neuroscientist at the Bioengineering Institute of Catalonia, said in a statement.

“But once the blood vessel is able to function again,” Battaglia said, “it begins clearing away Aβ and other harmful molecules, allowing the entire system to regain its balance.”

How did they do it?

Battaglia and his team developed nanoparticles that mimic a protein called LRP1, a molecule normally responsible for responding to toxins in the blood-brain barrier.

For the study, the researchers genetically engineered mice to produce more amyloid beta proteins and show significant cognitive decline similar to Alzheimer’s. Each mouse received three injections of the new drug, and the researchers observed changes in their behavior and brain activity for 6 months.

The results were impressive. The scientists found that a 12-month-old mouse (equivalent to a 60-year-old human) that received the treatment, when re-evaluated at 18 months (a 90-year-old human), “recovered healthy mouse behavior.”

“What is notable is that our nanoparticles act as a drug and appear to activate a feedback mechanism that restores the clearance pathway to normal levels,” Battaglia said. Surprisingly, it took only three injections for the treatment to reverse the progression of Alzheimer’s disease in mice, the researchers reported.

As with all mouse studies, it will take more work before this treatment can be tested for use in humans. But the results suggest that the approach, which essentially convinces the brain to return to a healthy state, could cure this otherwise incurable disease.