Studies show mixed success in Alzheimer's fight

By Julie Steenhuysen

CHICAGO (Reuters) - A new drug showed promise at treating Alzheimer's disease, but an experimental vaccine that cleared brain-clogging plaques failed to improve memory or help patients live longer, researchers said on Thursday.

One of two studies, conducted in Russia and published in the journal Lancet, showed Medivation Inc's drug Dimebon, first approved in Russia as an antihistamine, improved thinking processes and ability to function in patients with mild to moderate Alzheimer's disease.

A second showed that an experimental vaccine by Elan Corp and Wyeth known as AN1792 may have removed signature plaques from patients' brains, but they all developed severe dementia anyway.

Dimebon helped keep Alzheimer's from progressing for more than a year. "It's a strong signal," said Dr. Rachelle Doody of Baylor College of Medicine in Houston.

Doody said the drug helped improve five measures of memory and function.

It is not yet clear how the drug works, but Doody said it appears to protect the energy powerhouses in cells known as mitochondria, which are often destroyed in neurodegenerative diseases.

Medivation, which helped design the study, earlier this month said Dimebon significantly improved cognitive function in patients with Huntington's disease, which causes uncontrolled movement and loss of thinking ability.

If proven to work in a larger study, the drug could add to a limited pool of approved drugs, which include Eisai and Pfizer's Aricept, Forest Laboratories' FRX.N Namenda, Novartis' Exelon and Johnson & Johnson's Razadyne.

All affect message-carrying chemicals in the brain called neurotransmitters. The Medivation drug would offer a different approach. "It's a unique mechanism," Doody said by telephone.

TARGETING PLAQUE

A study by Dr. Clive Holmes of Moorgreen Hospital in Southampton in Britain involved six-year follow-up of AN1792. The vaccine was one of the first attempts to reverse formation of plaques in the brain associated with Alzheimer's.

Studies in mice showed immunization against a protein called amyloid beta helped remove plaques, but a study in humans was halted early because some patients developed severe brain inflammation.

Holmes and colleagues followed 80 patients who had been in the study. Tests showed no signs it had any effect on cognitive function. They also did autopsies on eight people who died. "In some cases there was a virtually complete removal of plaques," Holmes said in an e-mail.

But seven out of the eight, including those with virtually complete plaque removal, had severe end-stage dementia before death. "It strongly suggests that plaques are not sufficient on their own to account for disease progression," Holmes said.

Dr. Peter St George-Hyslop of the University of Cambridge said in a commentary, "This study will undoubtedly evoke concern that anti-amyloid therapies will be ineffectual, and that two decades of experimental work supporting their development were spent barking up the wrong tree."

While not a cure, he said the approach may still slow progression of the disease.

Elan and Wyeth now have hopes for bapineuzumab, an antibody drug that fights beta amyloid plaques, in late-stage clinical trials after success in some patients in a smaller study. Alzheimer's affects 26 million people worldwide.