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.