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'De-Tangling' Alzheimer's Drug Shows Promise
Date:7/29/2008

Patients' cognition improved as medication rid brain of matted protein, researchers say

TUESDAY, July 29 (HealthDay News) -- A drug that aims to reduce the clogging "tangles" in the brain cells of people with Alzheimer's disease appears promising in early trials, researchers report.

Further studies are necessary to confirm whether the medication is as effective at slowing Alzheimer's as it seems, or whether it needs to be given as part of a cocktail of treatments.

Still, the new findings are promising, said study lead author Claude M. Wischik, professor in mental health at the University of Aberdeen in the U.K., and chairman of TauRx Therapeutics, which is testing the compound. "The good news is that this is a breakthrough," he said. "A whole new, different approach has opened up against the odds, against people's expectations."

These and other findings into potential Alzheimer's treatments were expected to be released Tuesday at the Alzheimer's Association's International Conference on Alzheimer's Disease, in Chicago.

At issue in the TauRx study are proteins in the brain known as tau. If they work correctly, they act as the equivalent of rivets in the "railroad tracks" in brain cells, allowing communication between cells, Wischik said.

But in people with Alzheimer's disease, these proteins create untidy mats of fibers called "tangles" in the brain. The tangles are directly linked to dementia, while the effects of another factor in Alzheimer's -- bits of protein gunk called amyloid plaques -- are variable, he said.

"People could have lots of this stuff (amyloid) and still play lots of bridge," Wischik said, "but if you have a lot of aggregated tau in the brain, you can't find your way to the toilet."

The new study looked at a drug designed to reduce the number of tangles. The study was a Phase II trial, meaning it looked only at appropriate doses and effectiveness. A larger, Phase III trial -- the last of the three routine phases of research into a drug -- is scheduled to begin next year.

Researchers gave either the drug, known as MTC, or a placebo to 321 Alzheimer's patients in the United Kingdom and in Singapore for 24 weeks.

Wischik's group found that the drug stabilized the progression of Alzheimer's over 50 weeks.

"The data show an 82 percent of reduction in the rate which the disease progresses," Wischik said.

Dr. Sam Gandy, chairman of the Alzheimer's Association's National Medical and Scientific Advisory Council, said the new study results are indeed promising, and he added that another anti-tau treatment is in the works.

"They could potentially be part of a cocktail of anti-amyloid and anti-tau drugs that might be the way we eventually come around to treating Alzheimer's, trying to hit multiple steps (in disease formation)," he said. "This is the sort of approach that's been successful in treating HIV and cancer."

The finding comes on the heels of results from another tau-targeted Alzheimer's drug trial, released at the ICAD meeting Monday. In that study, led by Dr. Donald Schmechel of Duke University Medical Center, older adults with what's known as mild cognitive impairment received an experiment nasal spray peptide called AL-108.

Mild cognitive impairment is typically thought of as a potential precursor to Alzheimer's disease. In the Phase II study, patients who received high doses of AL-108 over 12 weeks gained "statistically significant, dose-dependent and durable improvement" in a variety of memory abilities, Schmechel said in an Alzheimer's Association news release.

In other findings released at the meeting Tuesday:

Researchers released detailed results of a Phase III trial of the drug tarenflurbil (Flurizan), which was targeted at reducing the sticky amyloid plaques in the brain. In June, the drug's manufacturer, Myriad Genetics, announced that the agent had failed to effectively treat Alzheimer's disease. The company is no longer developing the drug for the treatment of Alzheimer's.

According to the results of the trial, the drug did reduce plaques but was still no better at helping patients with mild Alzheimer's than a placebo, while causing more of some types of side effects.

On the other hand, a Phase II trial of a drug known as PBT2 did show some promising results. According to researchers at the University of California, Los Angeles, PBT2 is thought to reduce amyloid plaques by disrupting the interaction of chemicals in the brain.

The trial, which was also published online Tuesday in The Lancet Neurology, involved 78 people with mild Alzheimer's who got PBT2 or a placebo daily for 12 weeks. The agent did reduce levels of amyloid plaque in cerebrospinal fluid. People on the higher dose (250 milligrams) of the drug also showed significant improvements in certain mental tests compared to those on placebo, the team reported.

Finally, a study from food company Danone suggests that a nutrient-rich "medical food" called Souvenaid could help boost the formation of brain synapses and may reduce amyloid plaques in patients with mild Alzheimer's. The product contains nutrients such as choline and omega-3 fatty acids, thought to be conducive to brain health.

More information

Learn more about the disease from the Alzheimer's Association.



SOURCES: Claude M. Wischik, MB ChB, professor in mental health, University of Aberdeen, U.K., and chairman, TauRx Therapeutics, Singapore; Sam Gandy, M.D., Ph.D., chair, National Medical and Scientific Advisory Council, Alzheimer's Association, and professor, Alzheimer's disease research, Mount Sinai School of Medicine, New York City; Alzheimer's Association International Conference on Alzheimer's Disease, Chicago, July 29, 2008


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