New hope for Alzheimer's patients with arthritis breakthrough

12 April 2012

Rheumatoid arthritis sufferers have a built-in protection against Alzheimer's that could soon become a promising new treatment for the brain disease, it was revealed today.

The protein GM-CSF plays a role in the defective immune system response that leads to the arthritic disorder.

But it also marshals the immune system to remove harmful deposits in the brain that are linked to Alzheimer's.

Tests on mice showed that the protein could reverse Alzheimer's symptoms in just 20 days.

Scientists, who say they are "amazed" at the finding, believe the discovery could quickly lead to a practical new treatment for Alzheimer's, the most common form of dementia.

A laboratory-made version of GM-CSF called Leukine has been used for years to boost the immune systems of certain cancer patients.

Because its safety profile is already well known, it should not take long to convert into an Alzheimer's therapy.

The US scientists, from the Health Byrd Alzheimer's Institute at Florida State University, are now planning a pilot trial later this year that will put the theory to the test.

Patients with mild or moderate levels of Alzheimer's will be given the protein to see if their symptoms improve.

Lead researcher Professor Huntington 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."

It was already known that people with rheumatoid arthritis (RA), an auto-immune disease that attacks the joints, had a reduced risk of Alzheimer's.

Until recently, most experts assumed this was due to the anti-inflammatory drugs commonly given to RA sufferers. But recent clinical trials showed the drugs do not help Alzheimer's patients, putting the theory in doubt.

Prof Potter's team took a different tack by investigating immune system mechanisms in RA.

"Our findings provide a compelling explanation for why rheumatoid arthritis is a negative risk factor for Alzheimer's disease," said the professor, whose research is published online today in the Journal of Alzheimer's Disease.

Three RA proteins were studied in mice bred to develop the rodent equivalent of human Alzheimer's.

One, GM-CSF, proved most likely to be protective against the dementia condition.

The researchers then injected the protein into "Alzheimer's" mice, and normal old-age mice.

Other groups of Alzheimer's and normal mice were administered an inactive salt solution, to act as a comparison.

Behavioural tests confirmed that the Alzheimer's mice were suffering signs of memory loss by the age of 12 months.

After 20 days, the treated Alzheimer's mice were performing substantially better in tests measuring their working memory and learning ability than those not given the protein.

In fact, their memories were similar to those of normal aged mice

Even normal mice treated with GM-CSF performed slightly better than their untreated peers.

In contrast Alzheimer's mice injected with salt solution continued to do badly in the tests.

Dr Tim Boyd, another member of the Florida team, said: "We were pretty amazed that the treatment completely reversed cognitive impairment in 20 days."

The brains of GM-CSF-treated mice showed a more than 50% decrease in beta-amyloid plaques - sticky clumps of protein that build up in the brains of Alzheimer's sufferers and are a hallmark of the disease.

Memory restoration was accompanied by boosted numbers of scavenging immune cells known as microglia in the brain.

Microglia are the body's "refuse collectors" and have the job of getting rid of toxic substances.

The scientists believe GM-CSF stimulates microglia to attack and remove beta-amyloid deposits in the brain.

It may also have the added effect of enhancing connections between brain cells.

Dr Simon Ridley, from the Alzheimer's Research Trust, said: "Positive results in mice can be an important first step for any new treatment, and it's encouraging the team is already planning the crucial next stage of a trial in people. We won't know whether GM-CSF can help people with Alzheimer's until clinical trials complete.

"The worldwide burden of dementia is growing, with more than 35 million people now affected. Research is the only answer to dementia, we must support our scientists in their efforts to beat it."

An estimated 850,000 people in the UK have dementia, more than half of whom are diagnosed with Alzheimer's.

Dr Susanne Sorensen, head of research at the Alzheimer's Society, said: "This exciting research provides a possible answer to the long unexplained question of why rheumatoid arthritis could reduce the risk of Alzheimer's disease.

"Given that the identified protein is already available as a drug that is proven to be safe in humans, the time taken to develop an Alzheimer's disease treatment could be substantially reduced.

"However, we must not jump the gun. Much more research is needed before we can say for certain that the findings demonstrated in mice would also occur in humans."

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