Key Alzheimer's vaccine trial abandoned

14:32 04 March 02

NewScientist.com news service

Trials of what was the most promising vaccine against Alzheimer's disease have been dropped, after 15 patients developed symptoms of brain inflammation.

Elan Corporation's experimental vaccine, AN-1792, had been shown to clear amyloid beta plaques in animals. The plaques are characteristic of the brains of patients with Alzheimer's disease. Human safety tests conducted in 2000 suggested the vaccine was safe, and an international trial to investigate its effects on the immune system of patients with mild to moderate Alzheimer's disease was launched.

But, as reported by New Scientist in January 2002, the trial was suspended after four of 97 patients developed central nervous system inflammation. Symptoms typically appeared several weeks after the second injection, and since January, another 11 patients have become ill.

"Our decision to first suspend dosing, and now permanently discontinue dosing, remains in the best interests of the health and safety of patients," says Ivan Lieberburg, Elan's chief scientific officer. "We are hopeful that our alternative Alzheimer's approaches will continue to advance in development."

David Smith, professor of pharmacology at Oxford University and chairman of the UK's Alzheimer's Research Trust, says the abandonment of the trial is "very disappointing. I know of no other treatment being developed that will actually attempt to reverse the disease process, which is basically what Elan was hoping to do."

Inflammatory response

AN-1792 contains a synthetic form of beta amyloid protein - the main component of the protein plaques that form in the brains of Alzheimer's patients. In animals, the vaccine worked by stimulating an immune response to the protein.

Some Alzheimer's researchers feared that vaccinating against a protein that exists in the brain might produce the kind of side-effects found in the 15 patients. "In any vaccination, there's a risk of some inflammatory response," says Smith. "And when you're doing vaccinating against something that's already present in the brain, there's the worry that inflammation could happen."

Richard Harvey, director of research at the UK's Alzheimer's Society says he remains optimistic that stimulating the immune system to target amyloid beta could work safely.

Lieberburg speculates that the vaccine might have over-stimulated the immune response in some people. Injecting specific doses of beta amyloid antibodies, rather than stimulating the body to produce its own antibodies, might be a solution, he says.

Preventing Alzheimer's

Preventing Alzheimer's disease developing in the first place might be a more promising long-term approach, says Smith.

A recent prospective study of more than 1000 people in the US found that those with high blood levels of an amino acid called homocysteine had double the risk of developing Alzheimer's between eight and 11 years later. A high level of homocysteine indicates a low intake of B12 and folate. Previous work has shown that homocysteine can be toxic to nerve cells.

The US National Institute on Aging is now planning a trial of homocysteine-lowering vitamins in people with Alzheimer's.

But Smith thinks trials on people with mild memory impairment but without full-blown dementia should now be conducted. Each year, about one million older people in Europe develop memory problems that do not significantly impact on everyday life. Up to 80 per cent of these people develop Alzheimer's within five years, he says.

Emma Young

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