(CN) — Researchers have designed an experimental drug that appears to reverse key symptoms in the progression of Alzheimer’s disease, even in advanced cases, by cleaning a patient’s system of proteins that appear to contribute to the disease on a cellular level, according to a new study.
Researchers at Albert Einstein College of Medicine in New York used the drug and its cleaning capabilities to reverse and restore various symptoms of the disease in mice, for instance short-term memory loss and impaired walking.
“Discoveries in mice don’t always translate to humans, especially in Alzheimer’s disease,” lead author Ana Maria Cuervo said in a statement. "But we were encouraged to find in our study that the drop-off in cellular cleaning that contributes to Alzheimer’s in mice also occurs in people with the disease, suggesting that our drug may also work in humans."
Cuervo, co-director of the Institute for Aging Research at Einstein College, discovered the existence of this cell-cleaning process, known as chaperone-mediated autophagy (CMA), in the 1990s and has published 200 papers on its role in health and disease.
The new study, published Thursday in the journal Cell, explains that the drug works by bolstering a cellular mechanism that rids the system of unwanted proteins by digesting and recycling them.
CMA becomes less efficient as people age, which increases the risk that an accumulation of unwanted proteins in the brain will develop into insoluble clumps that damage cells. Alzheimer’s and all other neurodegenerative diseases are characterized by the presence of toxic protein aggregates in patient’s brains.
The study examines the dynamic interplay between CMA and Alzheimer’s disease, with loss of CMA in neurons contributing to Alzheimer’s. The results show that an increase in CMA through drug therapy appears to alleviate the symptoms of Alzheimer’s, even in advanced cases.
The findings conclude that drugs that increase CMA may help to alleviate Alzheimer’s symptoms. In studies with mice genetically altered to lack CMA in their brain cells, Cuervo and her team found that the absence of CMA was enough to limit short-term memory and impair the ability to walk, in addition to other problems frequently found in rodents with Alzheimer’s disease.
The absence of CMA also appeared to significantly affect the cells’ ability to regulate the proteins they contained. Proteins that would have been soluble shifted to being insoluble, increasing the risk of clumping and toxicity.
Cuervo suspected that early Alzheimer’s impairs CMA, so she and her team devised a study in mice that appears to confirm that CMA activity is somewhat inhibited in people with early stages of Alzheimer’s, followed by much greater CMA inhibition in the brains of people with advanced Alzheimer’s.
“By the time people reach the age of 70 or 80, CMA activity has usually decreased by about 30% compared to when they were younger,” Cuervo said. “Most peoples’ brains can compensate for this decline. But if you add neurodegenerative disease to the mix, the effect on the normal protein makeup of brain neurons can be devastating. Our study shows that CMA deficiency interacts synergistically with Alzheimer’s pathology to greatly accelerate disease progression.”
The new drug developed by Cuerva and her team and designed by Evripidis Gavathiotis, a professor of biochemistry and of medicine and a co-author on the study, appears to bolster CMA production in cells enough to reverse the damaging effects of increased proteins in the system.
“The sheer amount of defective protein in Alzheimer’s and other neurodegenerative diseases overwhelms CMA and essentially cripples it. Our drug revitalizes CMA efficiency by boosting levels of a key CMA component,” Cuerva said.
The new drug, called CA, works by enabling cells to bind to proteins in order to carry the proteins out of the system for recycling. CA restores protein receptors to youthful levels, according to Cuerva.
A separate study by Cuerva and her team published in Nature Communications earlier this month showed for the first time how loss of these receptors over time causes loss of CMA in humans, just as it does in animal models of Alzheimer’s.
“Importantly, animals in both models were already showing symptoms of disease, and their neurons were clogged with toxic proteins before the drugs were administered,” Cuervo said in the statement. “This means that the drug may help preserve neuron function even in the later stages of disease. We were also very excited that the drug significantly reduced gliosis – the inflammation and scarring of cells surrounding brain neurons. Gliosis is associated with toxic proteins and is known to play a major role in perpetuating and worsening neurodegenerative diseases.”
Treatment with CA did not appear to harm other organs even when given daily over extended periods of time, the researchers said.Follow @https://twitter.com/sabrinacanfiel2
Subscribe to Closing Arguments
Sign up for new weekly newsletter Closing Arguments to get the latest about ongoing trials, major litigation and hot cases and rulings in courthouses around the U.S. and the world.