From _The Wall Street Journal,_ July 18, 2012: *Immune Drug Shows Promise for Alzheimer's* By Shirley S. Wang A tiny but promising study suggests that a medicine used for immune disorders may offer long-term benefits to Alzheimer's patients—a result likely to spur demand for the treatment even though it is in limited supply and isn't approved for the memory-debilitating disease. The treatment, intravenous immunoglobulin therapy, or IVIG, is made from the blood plasma of healthy young adults. Since 2004 it had shown early promise for Alzheimer's, which afflicts some five million Americans. In the new study, four patients with a mild to moderate form of the disease who had been taking an IVIG drug for three years saw their cognitive ability and behavior stabilize, meaning their symptoms didn't get worse, said Norman Relkin, a neurologist at Weill Cornell Medical College in New York who presented the findings at the Alzheimer's Association International Conference in Vancouver, British Columbia. The finding is striking because people diagnosed with Alzheimer's typically see dramatic memory declines within 18 months, if not much sooner. The patients in the study used a version of IVIG from Baxter International Inc. called Gammagard. The results suggest Gammagard "is a viable long-term therapy in this group" of Alzheimer's patients, said Dr. Relkin. These new data represent the longest follow-up to date on patients from Baxter's midstage clinical trial. Earlier results were encouraging enough to prompt the company in 2007 to move Gammagard into late-stage testing for Alzheimer's. Results from this phase III testing are expected in early 2013. William Thies, chief medical and scientific officer of the Alzheimer's Association, a group that funds research into the disease, called the findings "tantalizing" but said more work is needed. Dr. Thies wasn't involved in the study. It is important to be cautious about the results due to the small sample size and because patients and investigators knew the patients were getting the medicine, which could have influenced the findings, said Rudy Tanzi, a neurology professor at Harvard Medical School. "We have to wait for a proper phase III [trial] before we reach a conclusion," said Dr. Tanzi, who wasn't involved in the study. "It's almost like a crapshoot; it's just too small to predict." Nevertheless, doctors who work with Alzheimer's patients said they expect patients and families to clamor for the drug. Many said they have been asked about Gammagard for years, and this latest positive result is likely to bring an increase. In February, when results in mice were published suggesting that a skin-cancer drug, bexarotene, was beneficial for Alzheimer's, many patients or their families started calling their doctors to ask whether they should use it off-label. A spokesman for Baxter said the company "does not support the use of its therapies for unapproved indications. Further, it remains difficult to monitor the use of our IG products for Alzheimer's disease." Drugs must be approved by the Food and Drug Administration for specific uses, but doctors can prescribe them for other purposes. With any off-label use, there are concerns about safety and efficacy. With Gammagard, there is an additional concern about supply. IVIG is costly and difficult to make. Baxter, one of several companies that make it, says it takes 130 plasma donations to make enough to treat one patient with primary immunodeficiency for a year. "The findings are highly promising but nevertheless a double-edged sword due to the limited supply," said P. Murali Doraiswamy, an Alzheimer's researcher at Duke University who wasn't involved in the study but previously served as an adviser to Baxter. "The growing off-label demand for Alzheimer's could threaten supply for immunodeficient patients." It isn't clear how the treatment helps Alzheimer's patients, but it appears to take advantage of antibodies from the plasma donors that combat a protein called amyloid, which clumps in the brains of people with the ailment. The drug is approved for a number of conditions, particularly diseases of the immune system, and many patients who use it have life-threatening conditions. Multiple companies make IVIG, but only Gammagard is in advanced clinical testing for use in Alzheimer's. Gayatri Devi, director of New York Memory Services, which treats patients with neurological conditions, has used Gammagard to treat Alzheimer's for about seven years. She says she started trying it after a patient's husband approached her in 2005 after hearing about an early clinical-trial result on TV. Dr. Devi has since treated several other patients with Gammagard, which involves lengthy office infusions every two to three weeks. She says she measures patients' functioning before starting treatment and six months later to see whether they should continue. She began with patients whose functioning seemed to be deteriorating significantly and more recently has started treating mild patients to see if she can slow the disease progression. About 70% of her patients have responded, to varying degrees, though none as significantly as her first patient, said Dr. Devi. But only about 5% of her patients can afford it, she said. It can cost more than $50,000 a year, and its use as an Alzheimer's treatment isn't covered by insurance."The jury is still out [about Gammagard], but there's a lot of evidence that suggests that something like this seems to help a significant proportion of patients with Alzheimer's who currently don't have any other available treatments," said Dr. Devi. The first patient, who had been diagnosed with the disease about eight years before she started Gammagard, had trouble walking and talking. Under Gammagard, the patient experienced impressive improvements in her language and movement, Dr. Devi said. Several of her patients have exhibited side effects. One developed a serious allergic reaction, two had kidney insufficiencies that reversed when they stopped and a few have had mild skin rashes that went away as they stayed on the treatment.