Doctors routinely use IVIG to treat a variety of infectious, immunological, and inflammatory conditions. The medicine is made from pooled plasma antibodies from donors, and among those antibodies are some that bind Aβ. People with Alzheimer’s possess unusually low levels of Aβ antibodies. IVIG is thought to work by promoting amyloid clearance and through its general anti-inflammatory effects. A previous Phase 2 study, led by Norman Relkin of Weill Cornell Medical College in New York City, suggested it could slow cognitive decline and brain atrophy (see ARF related news story), and several clinical trials are underway.

However, IVIG’s possible benefits come with a major potential caveat: The medication is expensive and in short supply, since it relies on donated plasma. If the treatment worked, Kile said, there would not be nearly enough of it to go around. In his study, therefore, he tried a shorter treatment course than others who have provided IVIG for 18 months or more to people who already have AD. Kile believed an early, brief therapy might suffice because in a previous study, scientists found that people who received IVIG treatment for reasons unrelated to AD were less likely to develop Alzheimer’s later (Fillit et al., 2009).

In Kile’s ongoing study, 52 people with MCI were evenly split between IVIG or saline placebo, receiving five doses spaced two weeks apart. Octapharma donated the IVIG but did not directly conduct the study. Kile used a dose of 0.4 gram IVIG per kilogram of body weight at each visit, based on the optimal dose from the earlier Phase 2 study led by Relkin. The total IVIG amount provided over the eight-week course matches standard dosage for IVIG treatment of neurological conditions such as the autoimmune condition Guillain-Barre syndrome, Kile said. He plans to follow the participants for two years. Thus far, 28 participants have hit the one-year mark, and Kile reported preliminary findings from that group in a poster at the meeting.

Comparing magnetic resonance images obtained at baseline and one year into the study, Kile observed that, while the placebo group lost an average of 8.8 percent volume, those on IVIG lost 5.7 percent, and the difference was statistically significant. “I was surprised; with a small ‘n’ we were able to show that,” Kile commented. Standard cognitive test scores changed little from baseline over the year. Based on the brain changes, Kile anticipates that cognitive decline may be noticeably slower in the treated group after more time has passed. This is at odds with immunotherapy results, where treated patients showed more atrophy than those on placebo, but it jibes with data from an MCI trial of B vitamins, which reported less atrophy in the treated group (Smith et al., 2010).

Magnetic resonance imaging showed that one year after treatment, people treated with IVIG (left) had less brain shrinkage than those on placebo (right). Image courtesy of Shawn Kile, Sutter Neuroscience Institute, Sacramento, California

The results confirm those of his earlier Phase 2 study, Relkin commented in an e-mail to Alzforum, although with a smaller effect on brain size. “If their final results prove to be consistent with these interim findings, it will likely spark a lively discussion about whether a short duration of IVIG is sufficient to obtain a meaningful therapeutic response in very mildly affected dementia patients,” he wrote. “A much larger study will be needed to draw firm conclusions about the use of IVIG in MCI.” (See full comment below.)

It is far too early to draw conclusions from Kile’s data, agreed Richard Dodel of Philipps University in Marburg, Germany, who has also worked with Octapharma’s IVIG (see ARF related news story on Dodel et al., 2013). He was skeptical that the final results would be positive. “This would be too good to be true,” Dodel put it. He also noted that change in brain volume is not a validated biomarker for AD, and it is not clear how that atrophy, or lack thereof, would affect thinking. “The cognitive measures are the most important measures at the moment,” Dodel said.

Kile’s group just completed dosing their last enrollee. As the study proceeds, he plans to analyze the rate at which people progress from MCI to full-blown AD.

Separately, researchers are also awaiting the results of a Phase 3 study of Baxter BioScience’s Gammagard® IVIG.—Amber Dance.