Alzheimer's Clue

A new study may help scientists unlock a medical mystery.  Researchers have found that rheumatoid arthritis patients seem to have protection from developing Alzheimer's disease.  The scientific link between the two may help researchers develop a new treatment for Alzheimer's.

Looking at pictures is just one way Bob and Donna Otten cope, after Bob was diagnosed with Alzheimer's disease four years ago. While looking through old photos, Donna explained "It'll help him recall what we saw, because he won't remember the trip all that well."

A new study from the University of Colorado may change that. "A protein that is released during rheumatoid arthritis into the blood seems to get into the brain and prevent Alzheimer's disease from getting hold." Dr. Huntington Potter, professor of Neurology at the University of Colorado told Ivanhoe.

The protective protein known as GMCSF is also an ingredient in the FDA approved drug leukine which is used to treat leukemia patients.

"This drug is very special because it seems to not only get rid of amyloid deposits in the brain but encourage the growth of new neurons." Said Dr. Potter.

The drug was studied in mice and found to be effective at halting Alzheimer's disease. Human trials are next.

For those with a family history of Alzheimer's, like the Ottens, the discovery could be life-saving  for future generations.

University of Colorado researchers will continue to study this new drug as a treatment for Alzheimer's but say definitive results are still a few years away.

RHEUMATOID ARTHRITIS: Rheumatoid arthritis (RA) is an autoimmune disease (a disease that occurs when the body's immune system mistakenly attacks its own tissues) and causes chronic pain and inflammation in various joints of the body. What makes rheumatoid arthritis different from other forms of arthritis is that it can appear in people of all ages rather than just people over 50, and multiple joints can be affected at the same time.  RA is a commonly diagnosed rheumatic disease and affects approximately 1.3 million people in the United States alone. It's also three times more likely to be found in women than men. No one yet knows what causes RA and there is currently no cure. (Source: www.medicinenet.com/rheumatoid_arthritis)

TREATMENT: There are a number of treatment options for RA that are primarily aimed at reducing inflammation and slowing the disease down to keep it from worsening. Doctors usually recommend over-the-counter nonsteroidal anti-inflammatory drugs (NSAID) such as ibuprofen and naproxen that focus on inflammation. Depending on the severity of the arthritis, these over-the-counter drugs may not be enough and require a prescription for a higher dosage or additional medication. In some severe situations, a doctor may prescribe steroids in order to ease pain caused by RA and can be taken as a pill. (Source: www.webmd.com/rheumatoid-arthritis)

NEW TECHNOLOGY: A new study is finding links between rheumatoid arthritis and Alzheimer's disease. Researchers at the University of Colorado have found that a protein released in the body from rheumatoid arthritis may be preventing Alzheimer's from forming in the brain. This protein is now being formed into a commercial drug called Leukine. So far, the drug has been tested on mice and shown to cut amyloid deposits in the brain in half and reverse cognitive problems. Researchers will now begin to test the protein on humans to see if it has the same effects but state that it will take a few years to have definitive results. (Source: http://www.sciencedaily.com/releases/2010/08/100822211549.htm)

FOR MORE INFORMATION ON THIS REPORT, PLEASE CONTACT:

Huntington Potter, PhD

Prof. of Neurology and Vice Chair for Basic Research

Director, Alzheimer's Disease Research and Clinical Center

Anschutz Medical Campus

University of Colorado, Denver MS 8608

huntington.potter@ucdenver.edu

If this story or any other Ivanhoe story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Marjorie Bekaert Thomas at mthomas@ivanhoe.com

Huntington Potter, PhD, Professor of Neurology, University of Colorado School of Medicine

Tell me about this study.

Dr. Potter: One of the things that's been interesting about Alzheimer's disease is that some people almost always get it and some people almost never get it. For example, people with Down's syndrome usually develop Alzheimer's disease by age 40-50 but people with rheumatoid arthritis almost never do. We considered the latter situation and began to look for something that might protect people with rheumatoid arthritis from developing Alzheimer's disease. What we found is that a protein that is released into the blood during rheumatoid arthritis seems to get into the brain and prevent Alzheimer's disease from gaining hold. This was proven in mice that develop Alzheimer's disease because this protein would reduce their amyloid deposits in the brain by half and completely reverse their cognitive deficit. The most interesting thing is that this molecule, a protein called GMCSF is a FDA approved drug already for people with bone marrow cancer. It had never been tried in Alzheimer's disease but since it seemed to work in the mice now we're testing it in people with Alzheimer's.

So people with rheumatoid arthritis produce this naturally?

Dr. Potter: Yes. It's a natural response to the inflammation that people with rheumatoid arthritis suffer from and doesn't seem to do them any good or any harm except that it protects them against Alzheimer's disease.

It's a drug that's already on the market for people with bone marrow transplantation?

Dr. Potter: Yes. What happens is that they need to stimulate their bone marrow to make more white blood cells and really boost their immune system and this drug helps them do that.

How was the study conducted where you discovered that this protein and the drug cures Alzheimer's in mice?

Dr. Potter: What we did was to look in the literature at everything that was different about people with rheumatoid arthritis. We made a long list and narrowed it down to one or two proteins that are released into the blood and then tested them in mice that have Alzheimer's disease. It turned out that GMCSF was able to reduce the amyloid deposits in the brain and return the mice to normal cognition in just a few weeks of treatment.

So how long had they had Alzheimer's?

Dr. Potter: These mice are genetically given Alzheimer's disease because they carry a human gene which, when mutant, causes human Alzheimer's disease, so they were essentially born with a predilection. We then tested them about six to eight months later when they were already beginning to show symptoms.

Explain the significance of the finding of this study.

Dr. Potter: The main significance is that this is a completely new approach to treating Alzheimer's disease that hasn't been tested before. It js based on an already FDA approved drug which is very safe and thus we can move quickly from the discovery in mice into humans.

Is this for anybody who has Alzheimer's?

Dr. Potter: That's the hope. People with Alzheimer's disease come in various different kinds. There are familial types in which you inherit the disease and then there's the sort that we call sporadic in which we don't know what causes it but it seems to be something that is in the environment such as your lifestyle or something else. We will be testing the typical age-related Alzheimer's disease first and then may test people with inherited Alzheimer's disease and people with Down's Syndrome.

Ideally it would actually reverse Alzheimer's and people would actually return to their normal cognition?

Dr. Potter: Ideally yes, except that the mice are very special in the sense that they do not lose the nerve cells that give us our cognition. It's easier to help them recover their full capacity.
Unfortunately people with Alzheimer's disease have already lost many neurons and they probably cannot be replaced. Our best hope would be that we could halt the disease in its tracks and let the patients continue their life the way they are now, which would be a tremendous advance.

So it would be huge for this to have early detection, early diagnosis right?

Dr. Potter: You make a very good point. All Alzheimer's drugs are assumed and very likely will work best in people at the very earliest stages before they have major pathology in the brain and before they have strong dementia, and this drug will also likely work best early in the disease.

Where will you go from here? What's the next step for you?

Dr. Potter: The next step for us is to recruit people into the clinical trial here in Denver at the University of Colorado and in a partner trial at the University of South Florida in Tampa. If these studies show positive affect and safety, then we could expand into a larger study.

At this point, you are not recommending people with Alzheimer's to go take this drug?

Dr. Potter: Absolutely not. The reason is that we don't even know yet whether it's safe in elderly people with Alzheimer's disease. They might be different from people needing a bone marrow transplant. It's also possible that it won't work, in which case you've taken a drug for no reason. It's really much better to let the scientists find out whether it works and whether it's safe so that we can go to the FDA and get approval. Then it will become available to the public. Science takes a little time and effort but in the long run it's worth it.

So would you say the jury is still out but you are hopeful? How do you feel about it at this point?

Dr. Potter: We're very hopeful but to be honest there have been other drugs that have worked in mice, perhaps not quite as well as this one, and then went on to be tested in humans and did not benefit people with Alzheimer's disease. This drug is very special because it seems to not only get rid of the amyloid deposits in the brain but is able to also encourage survival of neurons, and to promote new neuronal processes and new blood vessels. It may have extra benefit that the previous drugs did not.

Do you have anything else you would like to add?

Dr. Potter: Well I think the main thing from a public point of view is that scientists all over the world are trying very hard to find a drug for Alzheimer's disease, but it takes money, effort and political will.

So is there an expectation as far as timing?

Dr. Potter: That's a little difficult to predict. Our first pilot study will probably be finished in about a year, but it's not likely to be strong enough to show that GM-CSF really cures Alzheimer's disease or slows it down. A longer study would be necessary and for that so we're looking at several years before we know for sure.

This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.