Day: 08/29/2010

Rheumatoid Arthritis Protein Reduces Alzheimer’s Plaques In Mouse Model

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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.

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, Ph.D., Eric Pfeiffer Professor 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, Ph.D., who, together with Steven Bennett, Ph.D., 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 this year investigating GM-CSF (Leukine) in patients with mild or moderate Alzheimer’s disease.

The study appears in the Journal of Alzheimer’s Disease.

Vitamin D Deficiency Linked to Autoimmune Diseases

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Study Also Shows Lack of Vitamin D May Also Be Linked to Some Cancers

Aug. 23, 2010 — There is now biologic evidence to back up the belief that vitamin D may protect against autoimmune diseases and certain cancers.

A new genetic analysis lends support to the idea that the vitamin interacts with genes specific for colorectal cancer, multiple sclerosis, type 1 diabetes, and other diseases, says Oxford University genetic researcher Sreeram Ramagopalan.

The study is published in Genome Research.

When Ramagopalan and colleagues analyzed the binding of vitamin D receptors to gene regions previously identified with different diseases, they found evidence of increased binding for multiple sclerosis, Crohn’s disease, lupus, rheumatoid arthritis, colorectal cancer, and chronic lymphocytic leukemia (CLL).

“Genes involved in autoimmune disease and cancer were regulated by vitamin D,” Ramagopalan tells WebMD. “The next step is understanding how this interaction could lead to disease.”

Role of Vitamin D Supplementation

The role of vitamin D supplementation in preventing these diseases is also not well understood.

Exposure to sunlight is an efficient way to raise blood levels of vitamin D hormone, and food sources of the nutrient include oily fish like salmon, fortified milk, and other fortified foods.

But most people would have a hard time getting the vitamin D they need from food, and the increased use of sunscreen has reduced sun exposures.

By one recent estimate, as many as half of adults and children in the U.S. were deficient in the vitamin.

Current recommended daily vitamin D intake is 200 IU (international units) for those up to age 50; 400 IU for people 51 to70; and 600 IU for those over 70. Most experts say that these doses are too low.

Many experts, including Ramagopalan, say 2,000 IU of the vitamin may be optimal for preventing disease.

Blood levels of the vitamin are measured as 25-hydroxyvitamin D. Levels below 20 nanograms per milliliter are generally considered deficient.

Harvard School of Public Health nutrition researcher Edward Giovannucci, MD, says blood 25-hydroxyvitamin D levels of between 30 and 40 nanograms per milliliter may be about right for reducing the risk of autoimmune diseases and certain cancers.

While he says some people can reach these levels without supplementation, many others would need to take 1,000 to 2,000 IU of the vitamin a day.

“Based on what we know, I think it is reasonable to recommend that people maintain blood levels of around 30 nanograms per milliliter,” he says.

Unanswered Questions

But vitamin D researcher JoAnn E. Manson, MD, says it is way too soon to recommend taking much larger doses of vitamin D than are recommended.

Manson chairs the preventive medicine department at Brigham and Women’s Hospital in Boston and is principle investigator of a large U.S. study on vitamin D.

Still in the recruitment stage, the five-year, 20,000-person study will explore the impact of 2,000 IU of vitamin D on the risks for a wide range of health conditions, including cancer, heart disease, diabetes, hypertension, and depression. The study will also examine the effects of the fatty acid omega-3.

“I think it is important that we not leap ahead of the evidence in recommending high doses of vitamin D,” she says. “We will soon have a better understanding of the optimal doses of vitamin D and the optimal blood levels associated with the best balance of benefits and risks. But right now there are many unanswered questions.”

Virus Linked to Chronic Fatigue Syndrome

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Murine leukemia viruses (MLV), a family of retroviruses known to cause cancer in mice, may be linked to chronic fatigue syndrome (CFS), a study shows.

The full name of the virus is xenotropic murine leukemia virus-related virus. It is part of a family of viruses known as murine leukemia viruses (MLV), which is a type of retrovirus known to cause cancer in mice.

The new study, published in the Proceedings of the National Academy of Sciences, conflicts with some earlier studies. Several U.S. studies, including a recent report from the CDC and research done in the U.K. and the Netherlands, found no evidence of MLV in the blood of people with CFS. One recent study, however, found evidence of an MLV-related virus called XMRV in blood cells of patients with CFS.

The new study shows that 86.5% of 37 people with CFS had evidence of murine leukemia virus in their blood, as did 6.8% healthy blood donors.

“There is a dramatic association with CFS, [but] we have not determined causality for this agent,” said Harvey Alter, MD, chief of clinical studies and associate director for research in the department of transfusion medicine at the National Institutes of Health (NIH) Clinical Center in Bethesda, Md., at a news conference. “Other labs have not found this virus, so a dilemma at present is how to reconcile that some labs find the association and others do not.”

“We think it is in the patient populations, not the lab testing [contamination causing a false-positive lab result], but the latter has not been completely ruled out,” he says.

More Questions Than Answers?

Steve Monroe, PhD, director of the division of high-consequence pathogens and pathology at the CDC, tells WebMD that the new study “raises as many questions as it answers and there are still a lot of things about this virus that we don’t know.”

Andrew L. Mason, an associate professor of medicine at the University of Alberta in Edmonton, Alberta, Canada, says it’s time to act, not point fingers.

There have been several studies showing the presence of this virus in the blood of people with chronic fatigue syndrome and prostate cancer, but other studies have not found it.

“We don’t know why that is,” he says. “It is baffling, and we need to sort it out rather than ignore it. It’s there. Does it cause disease? We don’t know, but it’s there and that needs to be investigated.”

“There is only one way to prove or disprove XMRV’s role and that is to do a proper study with antiviral drugs,” Mason says. In an editorial accompanying the new study, he suggests studies that compare antiviral drugs with placebo or dummy pills on viral load and CFS symptoms in affected individuals are now feasible.

Such drugs are used to treat HIV, the virus that causes AIDS, and can cause several side effects.

“The drugs are well-tolerated, and we would be justified ethically to see if they work,” he tells WebMD. He likens this situation to the now Nobel-prize-winning research that first tested antibiotics to determine if some ulcers are caused by the bacterium H. pylori.

“We didn’t know that H. pylori was causative until they tried using medicine and it worked,” says Donnica Moore, MD, a women’s health expert and president of Sapphire Women’s Health Group in Far Hills. N.J.

The issue is a personal one for Moore, whose son was diagnosed with CFS about six years ago. As a result, she has become an outspoken advocate for research into the cause and cures for CFS. Moore is also a spokeswoman for the Whitemore Peterson Institute for Neuro-Immune Disease, the group that published a previous report linking XMRV and CFS.

“I hope this study puts to rest any question about the validity of the [findings] and will allow science to move on toward diagnostic, treatments, and causality studies,” she says.