Catalan researchers reverse Alzheimer's symptoms in mice with an injection

BarcelonaAn injection of nanoparticles can reverse the symptoms of Alzheimer's in mice genetically engineered to suffer cognitive decline similar to that caused by this dementia, which affects some 33 million people worldwide.

Researchers from the Institute for Bioengineering of Catalonia (IBEC) have co-led a preliminary international study that has developed a therapeutic strategy that restores the function of the brain's natural cleanup system and, in this way, eliminates the toxic accumulation of beta-amyloid protein between neurons.

The results they have obtained are, in the words of the researchers themselves, "very promising": just one hour after administering the treatment, the levels of toxicity in the rodents' brains had been reduced by 50%.

After three injections, the mice showed complete regression of the disease and had recovered cognitive ability similar to that of healthy mice of the same age. Interestingly, the results lasted the equivalent of 20 or 30 human years.

"Instead of targeting brain cells, as traditional treatments do, we focused on the cerebral vasculature," explains co-author Lorena Ruiz, a senior researcher at IBEC and Serra Hunter Professor at the University of Barcelona. "With smart nanoparticles, we have managed to reactivate the normal functioning of the cerebral vasculature to eliminate neurotoxic species responsible for the cognitive decline specific to the disease," she adds. This breakthrough could be a promising step toward an effective treatment for Alzheimer's disease.

Sweep away toxins

The brain has a natural cleansing mechanism that sweeps away toxins produced by neuronal activity every day, crossing the blood-brain barrier, a protective vascular wall that regulates the brain's environment, and depositing them in the blood so that the liver can eliminate them.

With dementia, and also with the aging process, this system, which involves a whole series of protein receptors responsible for transporting toxins out of the brain, begins to deteriorate until it stops working. As a consequence, the trash, such as beta-amyloid and tau proteins, begin to accumulate inside and outside neurons and cause brain damage. This is one of the defining characteristics of neurodegenerative diseases, specifically dementia.

What the IBEC researchers have done is design a switch—nanoparticles—capable of restarting the cleansing mechanism. These nanoparticles bind to beta-amyloid proteins and drag them across the blood-brain barrier into the bloodstream to begin the elimination process.

"What we do is remove materials from the brain that accumulate and cause damage," explains Icrea researcher Giuseppe Battaglia, from IBEC and who led the research, in an interview with ARA. Now, this scientist continues, it will be necessary to study the most ideal time to treat patients with these nanoparticles to obtain maximum efficacy, and whether they are equally potent in very advanced stages. "At the moment, we don't have an answer. But in the study, we treated animals with a very advanced state of cognitive impairment and we saw a very significant improvement," Battaglia points out.

To assess the therapeutic effects of the treatment, the researchers conducted experiments evaluating animal behavior and the rodents' memory for months, with the goal of covering all stages of the disease. Thus, they treated 12-month-old mice, the equivalent of a 60-year-old human, with nanoparticles, and only six months later the animal displayed behavior similar to that of a healthy rodent of the same age (18 months, equivalent to a 90-year-old person).

"In the long term, it appears that the treatment restores the brain's vascular system," Battaglia notes. Since toxic molecules do not accumulate, the disease does not progress, the vasculature returns to functioning and cleaning, and the system regains balance. This advance has been published in the journal Signal Transduction and Targeted Therapy.