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According to a New York-Presbyterian/Weill Cornell (NYPWC) study, a purified mixture of human antibodies called intravenous immunoglobulin (IVIg) provides lasting benefits to patients with Alzheimer's disease (AD). The clinical study is the first to demonstrate that IVIg stabilizes or improves cognitive function in patients with AD when administered over a period of a year or more. Results were announced at the International Conference on Alzheimer's Disease and Related Disorders (ICAD) in Madrid, Spain, in July 2006.


IVIg contains antibodies that bind to [beta]-amyloid (A[beta]), a central component of the plaque in the brains of patients with AD. It is believed that IVIg helps promote the clearance of A[beta] from the brain and blocks A[beta]'s toxic effects on brain cells. Approved by the FDA for treating several immune disorders, IVIg has been available for more than 30 years. It has been safely used in hundreds of thousands of patients. It has only recently been studied for the treatment of AD.


In a previously reported 6-month pilot study, the NYPWC team found that IVIg administration improved or stabilized the cognitive test scores of eight patients with mild to moderate AD. These patients subsequently declined when IVIg was stopped for 3 months. Investigators decided to resume IVIg at a low dose in a 9-month open-label extension study. IVIg was given every other week and was well tolerated by all eight patients. Six of the eight patients benefited clinically from the resumption of IVIg. Most patients with AD in the study remained at or above their baseline level of cognitive performance 18 months after they first received IVIg. Without treatment, AD is relentlessly progressive and usually causes measurable decline in thinking abilities over a comparable period of months.


In the NYPWC clinical study, IVIg administration transiently altered levels of [beta]-amyloid peptide in blood and caused a lasting decrease in [beta]-amyloid levels in spinal fluid. On average, spinal fluid [beta]-amyloid levels were reduced by about a third, consistent with the mobilization of amyloid out of the central nervous system and into the blood stream, where it is cleared from the body.


Dr Marc Weksler, the study's coprincipal investigator, said, "IVIg's potent effects on [beta]-amyloid levels in spinal fluid are certainly remarkable given the modest levels of antiamyloid antibodies it contains. It is possible that the wide repertoire of anti-amyloid antibodies present in IVIg as well as other effects on the immune system contribute to the clinical benefits."


Dr Weksler is the Irving Sherwood Wright Professor of Geriatrics and a professor of medicine at the Weill Medical College of Cornell University in New York City. Dr Weksler is also an attending physician at NYPWC.


Boosting the Power of IVIg

Dr Weksler and his colleague, Dr Paul Szabo, studied the properties of antiamyloid antibodies in IVIg as part of an effort to develop a more potent antibody preparation for patients with AD. At the ICAD in Madrid, the researchers reported that they have developed techniques to increase the amount and affinity of anti-[beta]-amyloid antibodies in IVIg.


The NYPWC researchers hope that enriching IVIg's antiamyloid properties may provide a means of increasing its potency as well as the available supply of human antiamyloid antibodies, as will be necessary for the millions of patients with AD worldwide. Translating these findings into an actual clinical treatment will require additional testing and development.


These studies were sponsored by grants from Baxter BioScience, the Elyachar Foundation, the Harvey Goodstein Charitable Trust, and the National Institutes of Health through a grant to the Weill Cornell General Clinical Research Center.


NYPWC Medical Center, located in New York City, is one of the leading academic medical centers in the world, composed of the teaching hospital New York-Presbyterian and its academic partner, Weill Medical College of Cornell University.