A purified mixture of human antibodies called intravenous immunoglobulin (IVIg) provides lasting benefits to patients with Alzheimer’s disease (AD), according to researchers at the NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The clinical study is the first to demonstrate that IVIg stabilizes or improves cognitive function in Alzheimer patients 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 today.

IVIg contains antibodies that bind to beta amyloid (A?), a central component of the plaque in the brains of Alzheimer’s patients. It is believed that IVIg helps promote the clearance of A? from the brain and block A?‘s toxic effects on brain cells. FDA-approved 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 Alzheimer’s.

In a previously reported six-month pilot study, the NewYork-Presbyterian/Weill Cornell 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 three months. Investigators decided to resume IVIg at a low dose in a nine-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.

“The majority of the Alzheimer patients in our study remained at or above their baseline level of cognitive performance18 months after they first received IVIg,” according to Basia Adamiak, who coordinated the IVIg open-label extension study at NewYork-Presbyterian/Weill Cornell. Without treatment, AD is relentlessly progressive and usually causes measurable decline in thinking abilities over a comparable period of months.

The study’s principal investigator is Dr. Norman Relkin, director of the Memory Disorders Program at NewYork-Presbyterian/Weill Cornell and associate professor of clinical neurology and neuroscience at Weill Medical College of Cornell University.

In the NewYork-Presbyterian/Weill Cornell clinical study, IVIg administration transiently altered levels of the 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 mobilization of amyloid out of the central nervous system and into the blood stream where it is cleared from the body.

“The persisting clinical benefits we see as IVIg decreases spinal fluid amyloid levels suggests that beta amyloid is the right target for the next generation of Alzheimer treatments,” says Dr. Relkin.

Dr. Marc Weksler, the study’s co-principal investigator, observes that “IVIg’s potent effects on beta amyloid levels in spinal fluid are certainly remarkable given the modest levels of anti-amyloid 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 professor of medicine at Weill Medical College of Cornell University in New York City. Dr. Weksler is also attending physician at NewYork-Presbyterian/Weill Cornell.

Boosting the Power of IVIg

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

“These techniques should allow the creation of more diverse and potent anti-amyloid antibodies from currently available IVIg products,” says Dr. Szabo, associate research professor of molecular biology in medicine at Weill Medical College of Cornell University.

The NewYork-Presbyterian/Weill Cornell researchers hope that enriching IVIg’s anti-amyloid properties may provide a means of increasing its potency as well as the available supply of human anti-amyloid antibodies, as will be necessary to meet the needs of the millions of Alzheimer patients worldwide. Translating these findings into an actual clinical treatment will require additional testing and development.

The NewYork-Presbyterian/Weill Cornell 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.

NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College