Hope for Alzheimer's vaccine

Hints emerge that doomed jab did some good.

22 May 2003

HELEN PEARSON

Elan's Alzheimer's vaccine trial was halted in January 2002. © GettyImages

A controversial vaccine may stall Alzheimer's disease, despite having serious side-effects, new research suggests. The study revives optimism that a tweaked version of the shot could reach the clinic.

Early hopes for the vaccine died in January 2002, when a handful of patients in a clinical trial of the treatment developed brain inflammation. The results forced Elan, the Dublin-based company behind the vaccine, to stop the tests.

Now a team led by Roger Nitsch of the University of Zurich in Switzerland has released the first data on how patients fared after immunization. Independently of Elan, the researchers monitored 30 patients in the clinical trial after it stopped¹.

Two-thirds of them did not deteriorate as expected, Nitsch's team found, on ratings that measure ability to dress, cook and lead normal lives. In memory tests, some "were even better than before the start of the study", says Nitsch.

Although the results must be confirmed in the remainder of the 372 trial participants, they suggest that a modified version of the vaccine might yet prove successful. "It revives hope" in the concept, says Alzheimer's researcher Bengt Winblad of the Karolinska Institute in Stockholm, Sweden.

Twist in the tale

Elan's vaccine aims to turn the body's immune system against accumulations of twisted protein called ß-amyloid in the brain. These unwanted clumps - called plaques - are characteristic of Alzheimer's disease and are thought to cause dementia.

Patients were injected with ß-amyloid to encourage the body to make antibodies against the protein. These should latch onto the plaques, tagging them for destruction by other immune cells.

Nitsch's group found antibodies against ß-amyloid in the blood of 20 of the 30 patients who were tested. Because the trial was 'blinded', the team does not yet know which were given the vaccine and which received placebo injections. But those that made antibodies are the ones most likely to have been vaccinated - and they showed the least deterioration.

Analyses at Elan have not found the same benefit in the entire set of patients, warns the company's chief scientific and medical officer, Ivan Lieberburg. "We have to be very cautious," he says.

But unlike Nitsch, Elan scientists did not investigate whether patients' antibodies actually bound to ß-amyloid plaques in brain slices. This might account for the difference, says Lieberburg. Similar experiments are now under way at Elan.

Brain power

Even if the vaccine is working, it is useless until scientists can understand and avert the life-threatening inflammation. They suspect that the presence of ß-amyloid fragments prompted inflammatory cells to attack the brain.

One way to solve this problem might be to snip off a portion of ß-amyloid that rouses inflammation, leaving intact the part that stimulates antibody production. Another could be to inject patients with ready-made antibodies against ß-amyloid.

Elan and other firms are investigating the approaches - both of which will require fresh clinical trials over several years. "I think this is getting exciting again," says Nitsch, " but anyone could get a side-effect and you're back to zero".

1. Hock, C. et al. Antibodies against ß-amyloid slow cognitive decline in Alzheimer's disease. Neuron, 38, 1 - 20 , (2003). |Homepage|