August 23, 2004

Decreasing Toxins in Brains of Alzheimer’s Patients Keep Cognitive Deficits at Bay

Pilot Study Shows that Selectively Draining Isoprostanes from Cerebrospinal Fluid
Stabilizes Cognitive Decline

(Philadelphia, PA) – The ever-slowing capacity to clear the build-up of such toxins as isoprostanes and misfolded proteins that accumulate in the brains of Alzheimer’s disease patients causes the death of cells involved in memory and language. Domenico Pratico, MD, Associate Professor of Pharmacology at the University of Pennsylvania School of Medicine, and colleagues have shown in a preliminary study that reducing the levels of isoprostanes, which specifically reflect oxidative damage in the brain, by draining cerebral spinal fluid (CSF) can stave off future reductions in cognitive abilities. This work appears in the August issue of the Journal of Alzheimer’s Disease.

As measured by a paper-and-pencil cognitive test, the researchers found that scores of the eight patients who had the specially designed shunt continuously operating for one year stayed stable. However, the scores of the patients who did not get the shunt declined by 20 percent after 12 months. “What’s interesting is that the patients without the shunt didn’t stop taking their regular Alzheimer medication, such as anti-cholinesterase,” says Pratico.

Over 12 months, the isoprostanes were reduced by about 50 percent compared to Alzheimer’s patients taking standard anti-Alzheimer oral medications alone. “We were very happy to see this amount of reduction,” says Pratico, who adds that the research team predicted reductions only half that size. Additionally, the normal components of CSF like glucose and immunoglobulins did not change after the shunt was placed in patients. The shunt has a selective capacity to filter out toxins of a specific molecular weight and size, in this case isoprostanes.

Applying a treatment for hydrocephalus to Alzheimer’s disease, the microns-wide shunt, or catheter, is placed subcutaneously in a space at the base of the cerebellum. It runs under the skin to the peritoneum, a space in the belly where body fluids accumulate before flowing to the kidney to be filtered and eventually eliminated in the urine. The shunt is put in once, drains continuously, and is cleaned out periodically by a neurologist.

The eight patients still have their shunts and there are now almost 100 patients recruited into the next phase of the study, which is being conducted at Stanford University. Other collaborators on this paper are: Yuemang Yao from Penn; Joshua Rokach, Florida Institute of Technology; Gerald G. Silverberg, Stanford University School of Medicine; Martha Mayo and Dawn McGuire, University of California, San Francisco Medical Center and Enroe Inc. This study was funded in part by the Alzheimer’s Association. Pratico has no financial interest in Enroe Inc.

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This release is available online at http://www.uphs.upenn.edu/news/News_Releases/aug/Alzheimersshunt.htm