Posted on 08/22/2010 3:55:50 PM PDT by decimon
New study shows GM-CSF reduces AD pathology and eliminates memory loss
Tampa, FL (August 23, 2010) -- A signaling protein released during rheumatoid arthritis dramatically reduced Alzheimer's disease pathology and reversed the memory impairment of mice bred to develop symptoms of the neurodegenerative disease, a new study by the University of South Florida reports. Researchers found that the protein, GM-CSF, likely stimulates the body's natural scavenger cells to attack and remove Alzheimer's amyloid deposits in the brain.
The study appears online today in the Journal of Alzheimer's Disease.
People with rheumatoid arthritis, a chronic disease leading to inflammation of joints and surrounding tissue, are less likely than those without arthritis to develop Alzheimer's. While it was commonly assumed that non-steroidal anti-inflammatory drugs may help prevent onset and progression of Alzheimer's disease, recent NSAID clinical trials proved unsuccessful for patients with Alzheimer's.
The USF researchers are among the first to look at what effect innate immunity gone awry in rheumatoid arthritis may play in protecting against Alzheimer's disease.
"Our findings provide a compelling explanation for why rheumatoid arthritis is a negative risk factor for Alzheimer's disease," said principal investigator Huntington Potter, PhD, professor of molecular medicine at the USF Health Byrd Alzheimer's Institute and director of the Florida Alzheimer's Disease Research Center.
"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."
The researchers analyzed three rheumatoid arthritis growth factors in mouse models and identified the signaling protein GM-CSF as the most promising for potential protective benefit against Alzheimer's disease. Then, they peripherally injected GM-CSF into two groups of mice – those genetically altered to develop memory problems mimicking Alzheimer's disease and normal, aged mice. Behavioral tests confirmed the Alzheimer's mice were exhibiting signs of memory impairment at age 12 months. Another two control groups of mice – the Alzheimer's mice and normal mice – were administered saline (placebo).
After the 10th day of injections, all the mice began a series of behavioral testing. At the end of the 20-day study, the cognitively impaired mice treated with GM-CSF performed substantially better on tests measuring their working memory and learning. In fact, their memories were similar to normal aged mice without dementia. Even the normal mice treated with GM-CSF performed slightly better than their untreated peers. The Alzheimer's mice administered 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, together with Steven Bennett, PhD, is a study lead author.
In addition, the brains of GM-CSF-treated Alzheimer's mice showed more than a 50-percent decrease in beta amyloid, a substance forming the sticky clumps of plaques that are a hallmark of Alzheimer's disease. This reduction in Alzheimer's plaques and associated restoration of memory was accompanied by more immune cells known as microglia in the brain. Microglia are like the body's natural garbage collection cells that rush to damaged or inflamed areas to get rid of toxic substances.
The researchers suggest that GM-CSF boosted during the immune system overdrive of rheumatoid arthritis helps harness the beneficial properties of inflammation in the brain. The protein may do this by recruiting more microglia from the peripheral blood into the brain to remove Alzheimer's plaques, Dr. Potter said. An apparent increase in neural cell connections in the brains of the GM-CSF-treated mice may also help explain GM-CSF's association with improving memory decline in Alzheimer's disease, the researchers said.
The USF Health Byrd Alzheimer's Institute plans to begin a pilot clinical trial later this year investigating GM-CSF (Leukine) in patients with mild or moderate Alzheimer's disease.
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Journal article (online): "GM-CSF up-regulated in Rheumatoid Arthritis reverses cognitive impairment and amyloidosis in Alzheimer mice;" Tim D. Boyd, PhD; Steven P. Bennett, PhD; Takashi Mori, DVM, PhD; Nikolas Governatori, BS; Melissa Runfeldt, BS; Michelle Norden; Jaya Padmanabhan, PhD; Peter Neame, PhD; Inge Wefes, PhD; Juan Sanchez-Ramos, PhD, MD; Gary W. Arendash, PhD, Huntington Potter, PhD; Journal of Alzheimer's Disease; Vol. 21:2 (August 23, 2010).
About USF Health
USF Health (www.health.usf.edu) is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida's colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, the University of South Florida is one of the nation's top 63 public research universities and one of only 25 public research universities nationwide with very high research activity that is designated as community-engaged by the Carnegie Foundation for the Advancement of Teaching.
About the Journal of Alzheimer's Disease
The Journal of Alzheimer's Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 3.83 according to Thomson Reuters' Journal Citation Reports (2010). The Journal is published by IOS Press (http://www.iospress.nl).
Ping
A lot of good things are going on at the University of South Florida, especially in the field of Neurology. This is tremendous news coming out of the Byrd Institute.
So maybe something good will come from RA.
My mother died of complications of Rheumatoid Arthritis. Although the disease is mostly know for its crippling effect on the joints, the inflammation can affect any part of the body, such as the major organs. When her lungs were affected, she was given massive doses of steroids in one last attempt to keep her alive. The steroids knocked out her kidneys. She died after about a year of dialysis.
Throughout all her agony, she remained sharp as a tack.
Now I see why.
Yes, RA is a terrible affliction..We need to pray that the human trials prove the success of GM-CSF in reversing Alzheimer’s. I believe the University of South FL is also doing some important research on Parkinson’s and ALS, which are both devastating neurological diseases.
My mother-in-law has both
They say that if trends continue that 30% of the population 65 and older will have Alzheimers. Since the percentage of elders is increasing, this poses a huge looming problem for society in the aging of the boomers. Hopefully, this will help address that particular problem.
She looks like she must have been a great mom. So sorry she’s gone...
She was in terrible pain when that picture was taken, which accounts for her slightly “fixed” expression.
oh my goodness, that sounds like me. My rheumatoid arthritis has attacked my lungs. My doctor caught it early and he keeps telling me that I’m lucky because my body responds so well to low dosages of steroids.
I always describe it as having your very own personal built-in torture chamber.
My lung scarring seems to have stopped, but it could always start again. I just wish they could come up with some treatment for the scarring.
I'd say that's an accurate description. I have AS (Ankylosing Spondylitis) which is a form of rheumatoid arthritis that's very difficult to treat, causes spontaneous fusion of the spine (the spine fuses itself) and attacks the major joints in the body. I've had 4 major back surgeries since my early 30's to correct the damage it's done, and I've had to have my knee's scoped out recently to "clean up" the mess the arthritis and AS have done to them. Doctor says it's also in my hips and elbows which will also likely require surgery in the next few years.
Personal torture chamber is right.......
I had to watch my mother suffer agonies with it for eight years. What a horrible disease. She was only 58 when she was diagnosed... very scary, as that’s only 7 years older than I am now.
"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,"
Let me get this straight. An ALREADY APPROVED drug might CURE Alzheimers? And since the drug is already approved for human use, it will be easy and cheap to test?
GET THOSE TESTS STARTED YESTERDAY.
That is amazing, we can only hope that it works.
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