The first report of long-term (three-year) stabilization of Alzheimer's disease symptoms with IVIG (Gammagard, Baxter), including no decline on measures of cognition, memory, daily functioning and mood, was reported at the Alzheimer's Association International Conference® 2012 (AAIC® 2012) in Vancouver.

Disappointing results from recent Alzheimer's clinical trials suggest that we may be testing therapies too late in the process of the disease – that once dementia symptoms are evident, too much damage has been done to the brain for effective treatment.

"Fortunately, improving detection technologies and updated diagnostic guidelines are enabling the detection of early changes in the brain and subtle cognitive deficits that are consistent with what is now known as presymptomatic (or preclinical) Alzheimer's," said William Thies, Ph.D., Alzheimer's Association® chief medical and scientific officer. "People in this stage of the disease are an ideal population for prevention trials to delay the onset or slow the progression of cognitive decline."

Intravenous immunoglobulin is being studied as an immunotherapy for Alzheimer's. IVIG is a blood product that is administered intravenously. Each dose contains pooled antibodies extracted from the plasma of more than 1,000 blood donors. IVIG is given to immune deficient patients who have decreased or absent antibody production capabilities to prevent infections. It is mainly used in immune deficiencies, autoimmune diseases, and acute infections.

Positive results of a placebo controlled Phase 2 study in mild to moderate Alzheimer's were previously reported. The 24 participants in that study received six months of treatment followed by a 12-month open-label extension where all subjects received IVIG. Several doses were tested.

To evaluate the long-term effects of IVIG, participants were offered additional IVIG treatment at a single standardized dose (0.4mg/kg every 2 weeks) for an additional 18 months. Sixteen of the originally enrolled subjects received treatment through month 36, including five originally given placebo and 11 treated with various doses of IVIG.

The researchers found that:

• Study participants who were treated with IVIG 0.4g/kg every two weeks for the full 36 months (n=4) had the best outcome, with no decline on several standard measures of cognition, memory, daily functioning and mood (ADAS-Cog, CGIC, 3MS, ADCS-ADL, NPI, QOL) at the three-year endpoint.
• As a group, the 11 participants who received IVIG for the full 36 months had favorable outcomes in terms of their thinking abilities, behavior and daily function.
• The five participants who were initially treated with a placebo and then switched to IVIG declined while on placebo but experienced less rapid decline while receiving a uniform dose of IVIG.

"Alzheimer's disease progresses over many years," said study leader Norman Relkin, M.D., Ph.D., of Weill Cornell Medical College, New York City. "It is crucial that we find effective, long-term treatments."

"This is the first study to report long term stabilization of Alzheimer's symptoms with IVIG. While the small number of participants may limit the reliability of our findings, we are very enthusiastic about the results. A Phase 3 trial is in progress and, in less than one year, we'll have more definitive data on the efficacy of 18 months of IVIG treatment."