A protein released in rheumatoid arthritis has been found to significantly reduce the progression of Alzheimer’s and actually reverse memory problems in mice engineered to develop symptoms of the disease, reports a new study by the University of South Florida.
Researchers think that the protein, GM-CSF, most likely stimulates the body’s natural scavenger cells to attack and get rid of amyloid deposits — a substance that forms the sticky plaque clumps in the brains of people with Alzheimer’s.
It is well known by scientists that people who suffer from rheumatoid arthritis are less likely than those without arthritis to develop Alzheimer’s disease. While it was previously assumed that the anti-inflammatory drugs prescribed for arthritis may have helped prevent onset and progression of Alzheimer’s disease, recent NSAID clinical trials have proven unsuccessful for patients who actually have Alzheimer’s.
The USF researchers are among the first to look at how the innate, overactive immunity found in people with rheumatoid arthritis may protect against Alzheimer’s disease.
“Our findings provide a compelling explanation for why rheumatoid arthritis is a negative risk factor for Alzheimer’s disease,” said Huntington Potter, PhD, Eric Pfeiffer Professor at the USF Health Byrd Alzheimer’s Institute, director of the Florida Alzheimer’s Disease Research Center and principal investigator of the study.
“Moreover, the recombinant human form of GM-CSF (Leukine) is already approved by the FDA and has been used for years to treat certain cancer patients who need to generate more immune cells,” Dr. Potter said.
“Our study, along with the drug’s track record for safety, suggests Leukine should be tested in humans as a potential treatment for Alzheimer’s disease.”
For the study, the scientists injected GM-CSF into two groups of mice — those engineered to develop memory problems imitating Alzheimer’s disease and normal, aged mice. There were also two control groups of mice — Alzheimer’s mice and normal mice — who were given saline (placebo). After 10 days of injections, all the mice began a series of behavioral tests.
When the 20-day study was over, the memory-impaired mice treated with GM-CSF performed much better on tests that measured working memory and learning. In fact, their memories were similar to the normal older mice without dementia.
Even further, the normal mice injected with GM-CSF performed slightly better than their untreated peers. The Alzheimer’s mice who had been given saline continued to do poorly on the tests.
“We were pretty amazed that the treatment completely reversed cognitive impairment in 20 days,” said Tim Boyd, PhD, who, along with Steven Bennett, PhD, is a lead author of the study.
In addition, the brains of GM-CSF-treated Alzheimer’s mice demonstrated more than a 50-percent decrease in beta amyloid deposits. There was also an increase in microglia — the body’s natural scavenger cells that rush to damaged areas and get rid of toxic substances.
The scientists suggest that because GM-CSF gets a boost during the overactive immune system in rheumatoid arthritis, more microglia are triggered, which in turn removes Alzheimer’s plaques, Dr. Potter said. In addition, there appeared to be an increase in neural cell connections in the GM-CSF-treated mice brains, and this may help explain GM-CSF’s link to reversing memory problems in Alzheimer’s disease, say the researchers.
The USF Health Byrd Alzheimer’s Institute plans to begin a pilot clinical trial this year researching GM-CSF (Leukine) in Alzheimer’s participants.
The study appeared online this week in the Journal of Alzheimer’s Disease.
Source: University of South Florida