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An implant for Alzheimer's

A shunt inserted in the brain to drain away toxins has shown early promise, but larger studies are still needed.

November 04, 2002|Jane E. Allen | Times Staff Writer

Alzheimer's research has yet to yield many useful therapies, even as the demand for treatments grows -- U.S. cases are expected to increase from 4 million to as many as 16 million by the middle of this century. A promising vaccine produced brain inflammation; medications that help patients function better during the early and moderate stages eventually lose ground to the incurable disease; and newer compounds to treat and prevent it remain years from reaching pharmacies.

So it's not surprising that scores of people with Alzheimer's are signing up to have shunts implanted in their brains, an invasive approach that has become one of the few bright spots in Alzheimer's research.

Dr. Gerald Silverberg, a Stanford neurosurgeon, reported last month that experimental shunts had slowed disease progression in a small group of patients. In that pilot study, published in the Oct. 22 issue of Neurology, he and his colleagues compared 12 patients with mild to moderate Alzheimer's who underwent shunt implantation with 11 Alzheimer's patients who received traditional care. After a year of monitoring and evaluation, the surgical patients remained stable; the comparison patients declined.

The shunts are designed to slowly drain away toxins from fluid bathing the brain and spinal cord. The initial study not only found the technique essentially safe -- no participants died or suffered permanent complications -- it also found lower levels of toxic protein fragments in shunted patients' brain fluid.

Although Silverberg hasn't formally monitored those he operated on three years ago, he said their families report they have not deteriorated. "They are still living at home, still functioning, still caring for themselves and don't require nursing home placement," he said. Such success is notable given the disease's usual progression. Silverberg formed a private company with three colleagues to produce and further test the shunt. An expanded trial, at 25 sites nationwide, aims to establish whether the device's apparent early success holds up. If it does, Silverberg said, "ours will be the first therapy that appears to alter the course of disease."

The early promise was enough for scores of patients desperate to slow or halt Alzheimer's inexorable decline.

Among them is John F. Harvey, an 83-year-old retired Air Force colonel diagnosed about 4 1/2 years ago. He underwent implantation of an experimental shunt in July at Southwest Texas Medical Center in San Antonio.

His wife, Lilas, said the two agreed to his participation because his physical health is excellent and his disease has been fairly stable for about three years; they're hoping to keep it that way. "The most important thing was that if he could be stabilized, then he would be able to stay home," Lilas Harvey said.

Because he's part of a randomized, placebo-controlled trial, Harvey doesn't know whether his shunt is working, or whether it's one of the comparison shunts that will remain closed for the first nine months of the experiment. After that, closed shunts will be opened so all participants can receive potential benefits.

The idea behind the shunt, Silverberg said, stemmed from observations that patients with hydrocephalus -- water on the brain -- had a high incidence of Alzheimer's. Both conditions involve decreased turnover of cerebrospinal fluid. Silverberg says that because their fluid is more stagnant, Alzheimer's patients have a hard time clearing out their excess of amyloid-beta protein fragments, called peptides. As a result, the peptides glom together and attach to brain cells, causing inflammation and damage.

By speeding up the elimination of fluid containing these peptides and allowing fresh fluid to take its place, the Stanford researchers hypothesized, patients might do better. They modified existing shunts -- narrow catheters commonly used in hydrocephalus -- with a low-flow valve that keeps fluid flowing at a constant rate, regardless of changing pressure inside the skull. So far, colleagues are waiting and watching.

The rationale behind the shunt procedure is valid and a larger trial is warranted, said Greg M. Cole, associate director of the UCLA Alzheimer's Disease Research Center.

Dr. Zaven Khachaturian, a medical and scientific advisor in Washington to the Alzheimer's Assn., said that, although surgery seems "a bit drastic," the work might lead to less invasive ways of addressing the problem.

"The general attitude is to be open-minded about any therapeutic approach because you don't know which ones will work," Khachaturian said.

Meanwhile, some researchers are focused on the use of neurotrophins, chemicals that can rejuvenate damaged brain cells; others are looking to the long-term potential of stem cells. Research projects also are studying the preventive potential of anti-inflammatory drugs, antioxidants and estrogen. And laboratories continue animal testing as they seek safer formulations of vaccines against the amyloid beta protein.

With the shunt trial, what's most important for patients, Cole said, is to find out "whether or not they're really stabilizing these people" and how much time the procedure will buy them and their caregivers.

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