Intravenous immunoglobulin and Alzheimer's disease: what now?

Intravenous immunoglobulin (IVIG) products are prepared from purified plasma immunoglobulins from large numbers of healthy donors. Pilot studies with the IVIG preparations Octagam and Gammagard in individuals with mild-to-moderate Alzheimer's disease (AD) suggested stabilization of cognitive functioning in these patients, and a phase II trial with Gammagard reported similar findings. However, subsequent reports from Octagam's phase II trial and Gammagard's phase III trial found no evidence for slowing of AD progression. Although these recent disappointing results have reduced enthusiasm for IVIG as a possible treatment for AD, it is premature to draw final conclusions; a phase III AD trial with the IVIG product Flebogamma is still in progress. IVIG was the first attempt to use multiple antibodies to treat AD. This approach should be preferable to administration of single monoclonal antibodies in view of the multiple processes that are thought to contribute to AD neuropathology. Development of "AD-specific" preparations with higher concentrations of selected human antibodies and perhaps modified in other ways (such as increasing their anti-inflammatory effects and/or ability to cross the blood-brain barrier) should be considered. Such preparations, if generated with recombinant technology, could overcome the problems of high cost and limited supplies, which have been major concerns relating to the possible widespread use of IVIG in AD patients. This review summarizes the recent AD IVIG trials and discusses the major issues relating to possible use of IVIG for treating AD, as well as the critical questions which remain.