Alzheimer's vaccine: human trial soon

By WILL DUNHAM

A new vaccine has blocked the development of Alzheimer's disease in mice genetically modified to carry the human gene for the degenerative brain disease.

Researchers at the New York University School of Medicine said they expected to test the vaccine in initial human clinical trials within a year.

They were optimistic that the vaccine would be safer than another one now being tested on humans.

"The potential for vaccination as a therapeutic approach for Alzheimer's disease is something that's very exciting," Dr Thomas Wisniewski, an author of the study, said.

"This is a particularly good line of investigation. And it looks like it will be translated very rapidly to human use."

Alzheimer's disease is characterised by the destruction of nerve cells, especially in the areas of the brain responsible for memory and learning.

Abnormal structures called plaques in the brain are one of the hallmarks of the disease. As the plaques accumulate, nerve cell connections are reduced.

The plaques are made up of deposits of amyloid beta protein, which is toxic to cells.

Dr Wisniewski and colleagues Dr Blas Frangione and Einar Sigurdsson injected the new vaccine into 11-month-old mice that had been genetically modified with a human gene for Alzheimer's disease.

At that age, the mice already had formed amyloid plaques in the brain.

Seven months later, the researchers examined the brains of the mice.

They found that the amount of amyloid plaque was reduced by 89 per cent in the cortex, the centre of higher thought, and by 81 per cent in the hippocampus, the memory centre, compared to the brains of mice that also had been genetically engineered but were not given the vaccine.

The vaccinated mice also had 57 per cent less of the protein that fosters the development of amyloid plaque.

The study appears in the American Journal of Pathology.

Four million Americans have Alzheimer's disease, including one in 10 of people over age 65 and nearly half of those over 85, says the Alzheimer's Association.

The group said that without a cure or prevention, the number would jump to 14 million by 2050.

Alzheimer's is a progressive, degenerative brain disease.

Its victims experience confusion, personality and behavior changes and impaired judgment.

Most people with Alzheimer's disease become unable to care for themselves.

The vaccine already in human clinical trials showed promise in mice less than two years ago.

That vaccine is made of a fragment of amyloid-precursor protein.

Dr Wisniewski expressed concern that the make-up of the first vaccine could be toxic to nerve cells in the brain and by itself may lead to the development of plaque.

In previous studies, the NYU team blocked the formation of amyloid plaque in the brains of rats by creating a short peptide, a fragment of a protein. This peptide prevented the formation of a toxic, insoluble form of amyloid that is deposited in plaques in the brain.

The new vaccine is based on a modified, nontoxic peptide.

"We believe that our peptide vaccine isn't toxic to nerve cells because it doesn't aggregate into clumps; it remains in solution," Dr Frangione said.

Dr Wisniewski said he hoped the new vaccine could be "a much more appropriate choice for future human studies" than the one already being tested. He said the NYU team was looking for a corporate partner as the vaccine moves into human trials.

"The hope here in particular is that this will work well because the effect in the animal model is so dramatic, and also because the amyloid lesions that you have in the animals are so similar to what you have in humans," Dr Wisniewski said.

- REUTERS