FRIDAY, April 22 (HealthDay News) -- Regular infusions of plasma   derived antibodies appear to reduce levels of Alzheimer's disease-causing brain plaques while improving patients' thinking ability, researchers report.

Buildup of beta-amyloid protein plaques in the brain is a hallmark of Alzheimer's and toxicity related to this buildup is thought to be a major cause of the disease, for which there is currently no effective treatment.

In this phase I clinical study, conducted by a team from New York-Presbyterian Hospital/Weill Cornell Medical Center, researchers gave patients with mild to moderate Alzheimer's periodic infusions of a targeted antibody, called immunoglobulin (IVIg). The antibody makes its way to the brain where it targets beta-amyloid for removal.

The study included eight Alzheimer's patients treated with IVIg. After six months of treatment, seven of the patients underwent cognitive testing. The tests showed that cognitive function stopped declining in all seven patients and had actually improved in six of the seven patients.

"If these results are confirmed in larger, controlled trials, we might have a safe Alzheimer's treatment capable of clearing the amyloid protein away," senior researcher Dr. Marc E. Weksler said in a prepared statement.

The study was presented at the recent annual meeting of the American Academy of Neurology in Miami.

The researchers emphasize that it's too soon to describe IVIg as anything more than promising, and they do not recommend that doctors treat Alzheimer's patients with IVIg at this point in time. Preparations are already underway for a larger, controlled Phase II clinical trial of IVIg, the researchers said.

IVIg is an antibody product derived from human plasma. The U.S. Food and Drug Administration has long approved the use of IVIg to treat other conditions, but not Alzheimer's.

It has been well known that Alzheimer's causes beta amyloid deposits in the brain. Antibodies against beta amyloid can be measured in C.S.F. these antibodies are reduces in patients who go on to develop Alzheimer's.  IVIg contains these antibodies so it is no miracle that it helps stop the disease in its track.

 

What is IVIg? IVIg stands for IntraVenous Immunoglobulin. It is a product of human blood that is derived from the plasma of thousands of healthy volunteers. IVIg contains antibodies, which are the proteins that help protect the body against disease.

Why is IVIg being studied as a treatment for Alzheimer's? It was recently discovered that IVIg contains antibodies that bind to beta amyloid (A¤). A¤ is a protein that many scientists believe is important in causing Alzheimer's. IVIg may help to promote the clearance of A¤ from the brain and block A¤'s toxic effects on brain cells.

Is IVIg a new treatment? IVIg was originally approved by the U.S. Food and Drug Administration for treating immune disorders and has been available for more than 30 years. IVIg is FDA-approved for the treatment of patients with primary immunodeficiencies, immune thrombocytopenic purpura (ITP), B-cell chronic lymphocyctic leukemia (CLL), Kawasaki syndrome, and immunodeficiency associated with pediatric HIV and bone marrow transplantation.

Neurologists also use IVIg in the treatment of multiple sclerosis and motor neuropathy, though IVIg is not approved for these conditions. It is--not currently approved to treat Alzheimer's disease, but is under study for that purpose.

How is IVIg treatment given? IVIg is administered by an infusion into a vein, a process that typically takes several hours. It is believed that infusions have to be carried out at least once or twice a month in Alzheimer's patients.

Is IVIg safe? Several hundred thousand persons have received IVIg over the years, and it is generally well-tolerated. There may be added risks to its use in elderly individuals with Alzheimer's, but many older persons have received IVIg without difficulty.

Because it is derived from human plasma, IVIg carries with it a very small risk of communicable diseases such as Hepatitis and HIV. However, in the United States there have been no documented cases of transmission of these diseases by IVIg over the past 10 years.

Other possible risks relating to use of IVIg include kidney failure, stroke, lung problems, heart failure, allergic reactions and other problems. The likelihood of these complications occurring can be reduced by screening out persons who have known risk factors and administering the IVIg in modified forms.

Is IVIg costly? IVIg is very expensive compared to medications currently in use to treat Alzheimer's disease. One month of treatment typically costs $5000-$10,000---- including the expense of the IVIg itself, the infusions and other costs.

How effective is IVIg in Alzheimer's? So far, only two clinical studies have been carried out examining the effects of IVIg in Alzheimer's disease at a mild to moderate stage of the illness. Collectively, a total of 13 patients were treated in these two studies, which is too small a number to establish whether or not the treatment works. IVIg was well-tolerated by the AD patients treated and none were noted to decline in their thinking abilities over 6 months of treatment. A majority of the patients improved on simple measures of thinking ability.

Many more persons with Alzheimer's will need to be treated in blinded studies that incorporate placebo controls before the usefulness of IVIg can be determined.

There are different "brands" of IVIg. Are they all the same? The various manufacturers of IVIg use different preparation processes, which could affect the usefulness of their product for treating Alzheimer's. The various brands of IVIg have not yet been compared in actual Alzheimer clinical trials, so it is not known whether they are all equivalent. Products made by Baxter Healthcare and Octapharm have been tested and both yielded positive effects.

How long will IVIg need to be given if it proves effective in treating Alzheimer's? It is not known how long treatment will need to be continued at this time.

Can my doctor prescribe IVIg for Alzheimer's? In theory, since IVIg is commercially available, it can be prescribed by a licensed physician. However, since the optimal dosing, preparation and patient for this treatment have yet to be determined, it is--not recommended that physicians use IVIg for this purpose at this time except in experimentally controlled clinical studies (trials). Since it is not approved to treat Alzheimer's disease, Medicare and third-party payers may choose not to pay for this treatment.

Office of Public Affairs NewYork-Presbyterian Hospital/Weill Cornell Medical Center 525 East 68th Street, Box 144 New York, NY 10021

Caution urged in Alzheimer's study
Much more research is needed, doctors say, into the effectiveness of arthritis drug Enbrel.
By Shari Roan, Times Staff Writer
June 26, 2006


Reports of success in treating Alzheimer's disease using injections of the arthritis drug Enbrel have sparked hope among Alzheimer's patients and their families — and some concern among physicians.

A recent study reported improvement in cognitive symptoms among 15 Alzheimer's patients who received weekly injections of Enbrel for six months. But doctors not involved in the research say the publicity surrounding it could lead Alzheimer's patients or their family members to believe Enbrel is a proven treatment for the disease when the study actually reflects interesting, but preliminary, research.

The pilot study was published in April by Dr. Edward Tobinick of Institute Research Associates in Los Angeles, along with three co-authors, in the peer-reviewed, electronic medical journal Medscape General Medicine.

The research explored whether Enbrel can reduce the activity of an inflammation-producing substance called tumor necrosis factor-alpha in the brains of Alzheimer's patients.

The 15 patients were injected in the back of the neck, above the spine. The study cited "a sustained and significant improvement in cognition" in both mild and more severe cases.

But Alzheimer's experts who were not involved in the study say it's too early to determine if the therapy offers real benefits because it was a small pilot study. They said a randomized, controlled trial was needed, in which some patients receive the drug and some do not, while the investigators remain unaware as to who is receiving medication.

"It's an uncontrolled study; that's important because many studies which look promising in an open study end up not being successful," says Dr. P. Murali Doraiswamy, a Duke University psychiatrist who is on the Alzheimer's Foundation of America's medical advisory board. "The study is too small for any reasonable conclusions to be drawn."

The concept behind the study — using a novel route to deliver an anti-inflammatory drug — is intriguing, says Doraiswamy. But previous research using other anti-inflammatory drugs in Alzheimer's patients has failed, he says. The Alzheimer's Foundation of America does not advocate the use of anti-inflammatory drugs because of the lack of evidence that they work.

Moreover, anti-tumor necrosis factor medications, including Enbrel, have been associated with rare but serious side effects, says Dr. George Bartzokis, a neurology professor and director of the clinical core of the Alzheimer's Disease Research Center at UCLA. Enbrel is linked to infections and symptoms of multiple sclerosis.

Experts also questioned whether the drug could reach the brains of patients. Tobinick says he injected it in the neck for closer proximity to the brain.

"The delivery of this drug is fairly unusual," says Freddi Segal-Gidan, a gerontologist and co-director of the Rancho Los Amigos-USC Alzheimer's Disease Research Center. "We have what is called a blood-brain barrier that is to protect the brain from agents getting in. It's unclear how much of this agent was able to get into the brain."

Tobinick, however, called the positive results "unprecedented" and says he is eager for other researchers to test the therapy.

"We would argue that this is urgently necessary due to the unmet medical needs being addressed and the degree of clinical improvement which was observed and documented," he says. "The degree of improvement and duration of improvement over six months both argue against … a placebo effect."

Tobinick, a dermatologist and internist, holds patents for his Enbrel treatment methods and owns stock in Amgen Inc., which makes Enbrel. He offers Enbrel to selected Alzheimer's patients outside of clinical studies..

The other three co-authors of the Alzheimer's paper have no financial interest