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Thread: Alzheimer's Vaccine Had Mixed Results/The Good and Bad of Experimental Alzheimer's Vaccine

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    Senior Member Max's Avatar
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    Alzheimer's Vaccine Had Mixed Results/The Good and Bad of Experimental Alzheimer's Vaccine

    Alzheimer's Vaccine Had Mixed Results
    2 hours, 54 minutes ago Add Health - AP to My Yahoo!

    By RANDOLPH E. SCHMID, Associated Press Writer

    WASHINGTON - The experimental vaccine withdrawn from testing after four Alzheimer's patients developed brain swelling seems to have reduced the accumulation of brain plaques associated with the disease but may have caused the dangerous inflammation, researchers report.

    The vaccine did not show success against another sign of the memory-destroying disease, tangled nerves and microfibers, according to the first autopsy results of one of the affected patients in the clinical trial. The 72-year-old woman died almost two years after first receiving the vaccine in July 2000.

    The 360-patient trial was halted in January 2002 and the drug, AN-1792, made by Elan Corp. of Ireland, was withdrawn after the inflammation known as meningoencephalitis was found in four subjects. Doctors later discovered 11 more people with the symptoms.

    Doctors at the University of Southampton in England report that the autopsy results show that the swelling "is likely to be a consequence of the immunotherapy."

    The vaccine had shown good results in mice, eliminating with few side effects the brain-damaging plaques called beta amyloid.

    The accumulation of plaques associated with Alzheimer's seemed to have been cleared from large areas of the human patient's brain, they said. But they found no reduction in the tangled nerves and microfibers also present in the disease.

    "That really couldn't have been predicted from the mouse studies because the mice develop only plaques and not tangles as they age," said James A.R. Nicoll, lead researcher on the report, appearing in Monday's online edition of the journal Nature.

    "In Alzheimer's disease (news - web sites) in general, we really don't know how much it is the plaques or the tangles that contribute to the brain dysfunction and dementia - or even if it is neither directly but that the dementia is due to loss of neurons or synapses from the brain," he said.

    The findings may give researchers a start to answering some of those questions, Nicoll said. "This is the first time we have been able to separately affect plaques and tangles," he said.

    Alzheimer's affects about 4 million people in the United States, and the number is expected to climb to 14 million by 2050 as the population ages.

    The disease was first described in 1906 by German doctor Alois Alzheimer and researchers have long sought a vaccine to combat it.

    There were high hopes for the vaccine when Elan d began testing, based on the results with mice.

    In initial tests, humans had no adverse effects. But because the vaccine works by inducing the immune system to attack the protein that makes up those plaques, some scientists had warned that brain inflammation was a potential serious side effect.

    After halting the trial, Elan ended development of the drug, though the company said it still hopes to produce a vaccine for Alzheimer's using other approaches.

    Bill Thies of the Alzheimer's Foundation said the paper is important because it indicates that the vaccine worked in helping remove plaques. That answers a vital question, whether a human given vaccine will generate enough antibodies to change the plaque concentration. "Clearly the answer is yes," said Thies, foundation vice president for scientific and medical affairs.

    The autopsy results "suggest an astonishingly powerful effect of the vaccination" on removing plaques, added to a commentary by researchers at Massachusetts General Hospital who were not participants in Nicoll's report.

    But the data do not prove the effectiveness of the vaccine because it remains unknown if the symptoms improve after the drug's use, said the commentary by S.M. Greenberg, B.J. Bacskai and B.T. Hyman.

    The woman autopsied had a five-year history of progressively worsening confusion and disorientation. She received her first vaccine in July 2000 and this was repeated after four, 12 and 24 weeks.

    A fifth injection was given at 36 weeks, using a reformulated vaccine. Six weeks later she suddenly had dizzy spells, drowsiness, unstable walk and fever, deteriorating to the point where tests could not be performed on her. She lived another year but showed no improvement in that time.

    Nicoll said there is no way to determine if the reformulated vaccine caused her sudden deterioration until other patients in the study have died and their brains are examined.


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    Senior Member Max's Avatar
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    The Good and Bad of Experimental Alzheimer's Vaccine

    The Good and Bad of Experimental Alzheimer's Vaccine
    15 minutes ago Add Health - HealthScoutNews to My Yahoo!

    By Amanda Gardner
    HealthScoutNews Reporter

    SUNDAY, March 16 (HealthScoutNews) -- In possibly the first case report of its kind, researchers have found an experimental vaccine for Alzheimer's disease (news - web sites) did wipe out the structures that are the hallmark of the condition, but apparently also caused the patient's brain to swell.

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    The 72-year-old woman studied was one of 360 Alzheimer's patients involved in a clinical trial of the vaccine, which was halted after 15 people developed brain swelling. The woman actually died of a pulmonary embolism a year after her last dose of the vaccine, which allowed researchers to autopsy her brain for clues on the vaccine's effectiveness.

    Most of the amyloid plaques, which are protein clusters whose buildup appears to cause Alzheimer's, had been cleared from the woman's brain, although other evidence of the disease remained, they found.

    "In that sense, it looks exactly as you predicted it might from previous studies of mice," says Dr. James A.R. Nicoll, the lead author of a report on the case in the April issue of Nature Medicine and a professor of neuropathology at Southampton General Hospital in the United Kingdom.

    On the other hand, it appears the vaccine, known as AN-1792, may also have caused meningoencephalitis, or swelling of the brain.

    Although the report deals with only one person, it could prove useful in pinpointing the future direction of research on this devastating disease, which currently affects 4 million Americans.

    "It's the first-ever report of its kind," says Bill Thies, vice president for medical and scientific affairs at the Alzheimer's Association. "It's very important from the standpoint that it leads us to believe that there has been a change in amyloid accumulation in a living person. That's something that no one has been able to demonstrate before. I think that this is just the leading edge that's going to come from that trial."

    Although numerous changes have been noted in the brains of patients with Alzheimer's disease who have died, scientists are not sure which of the changes are responsible for the loss of memory and other cognitive deficits that are classic symptoms of the disease. In recent years, much research has focused on the amyloid structures as the likely cause.

    That's why this new research is so important, according to Thies. "If you look across the spectrum of Alzheimer's investigators, half or more work is on amyloid. And if that's not going to be a fruitful pathway, we ought to make some adjustments," he says. "We're trying to find out if this is the right way to go."

    Because the woman died, one of the pivotal questions in Alzheimer's research remains unanswered.

    "While the vaccine was effective in perhaps limiting amyloid accumulation, we don't know whether it had any effect on disease process, and that's a very important question," Thies says.

    According to the researchers, the woman received her first injection in July 2000. That dosage was repeated four, 12 and 24 weeks later with no apparent problems. She received a fifth injection with a different dosage 36 weeks after the first injections. Six weeks later, she developed dizzy spells, drowsiness, fever and an unstable gait.

    The woman died in February 2002, a month after researchers decided to halt the trial, which was conducted in Europe and the United States. The remaining trial participants are being carefully followed and evaluated, and Thies estimates that their data will be analyzed sometime this summer.

    "We do know from some work that's been reported from a couple of the centers that were part of the trial that a portion of the people who are in the trials seem to be still busily making antibodies to amyloid, which is the way we think this treatment works," Thies says.

    Meanwhile, researchers involved in the trial are trying to come up with ways to eliminate the side effects of AN-1792.

    "Immunologists seem quite confident that it will be possible to develop an approach that gives the good affect of removing the plaques without the bad affect of the inflammation," Nicoll says. "They seem quite confident that they can modify the substance that is injected and get the good without the bad."

    And if that happens, still one more question needs to be answered: Can that or any vaccine, given to younger people, actually prevent Alzheimer's from developing?

    That remains the holy grail of Alzheimer's research.

    More information

    For more information, visit the Alzheimer's Association or the National Institute of Neurological Disorders and Stroke.

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