Caution urged in Alzheimer’s study

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.

He also uses Enbrel injections to treat chronic back pain, an approach that is the subject of a class action lawsuit, in final stages of settlement, over alleged misleading and deceptive advertising. He has been charged by the Medical Board of California with, among other things, misleading advertising and misrepresentation of the treatment.

The other three co-authors of the Alzheimer’s paper have no financial interest in Enbrel or the delivery method.

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For more information on Alzheimer’s disease treatments, contact the Alzheimer’s Assn. at www.alz.org or (800) 272-3900, or the Alzheimer’s Foundation of America at www.alzfdn.org or (866) 232-8484.