Abstract
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.
Highlights
The severity of the Alzheimer’s disease (AD) problem in the US is indicated by recent statistics from the Alzheimer’s Association [1]
As of this writing (May 2013) it is unclear whether any Intravenous immunoglobulin (IVIG) products will offer a breakthrough for treatment of AD. Because these preparations differ in their concentrations of antibodies to Aβ [10,11,12] and tau protein [13], there may be differences between them with regard to their efficacies in AD. This purpose of this review is to summarize the IVIG AD trials conducted to date, the issues raised by the potential use of IVIG for treatment of AD, and critical questions which remain
We recently reported the presence of antibodies to recombinant human tau, which is unphosphorylated, in IVIG products [13]
Summary
The severity of the Alzheimer’s disease (AD) problem in the US is indicated by recent statistics from the Alzheimer’s Association [1]. Renal problems Renal dysfunction, acute renal failure, and osmotic nephrosis can result from IVIG treatment in patients with predisposing conditions such as renal insufficiency, diabetes mellitus, age > 65, volume depletion, sepsis, or receiving nephrotoxic drugs [24,25] This is true for IVIG products that use sucrose as a stabilizing agent. Polyclonal anti-D, a type of IVIG consisting of plasma from RhD-negative donors immunized to the D antigen [78], has been used to treat idiopathic thrombocytopenic purpura [79,80], and Shoenfeld and colleagues [81] have generated specific IVIG (sIVIG) preparations for a number of immune-mediated conditions including lupus and antiphospholipid syndrome These antibodies could be produced with recombinant technology to avoid potential supply difficulties. Does IVIG treatment of AD patients increase their risk for microhemorrhage? (In the phase II Octagam study, 14% of the Octagam-treated patients had microhemorrhages vs. none in the placebo group [8])
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
