Can a jab keep brain trouble away?

A vaccine developed to fight brain disorders such as Parkinson’s disease has shown promise in preliminary animal trials. But experts caution that the positive results may not translate into an effective treatment for humans. The formation of abnormal protein aggregates in the brain, known as Lewy bodies, has been linked to several neurological disorders in adults. These include Parkinson’s disease, a condition that can involve slow movements, tremors and impaired coordination. Genes may predispose someone to the disease, say researchers. Others point to environmental toxins as a potential trigger.

Whatever the cause, doctors currently lack a cure for Parkinson’s disease and related Lewy-body illnesses. Many think that getting the immune system to attack the protein aggregates is a good step towards finding a treatment. So several research teams have been pursuing therapeutic vaccines. Biologists have already succeeded in giving mice specially designed immune cells to save them from neurological damage. Now they have gone a step further by getting mice to produce their own immune protection through a series of injections.

The vaccine, developed by Leslie Crews of the University of California, San Diego, and colleagues, is based on the protein in Lewy bodies, known as alpha-synuclein. An overdose of this protein, which acts at the tips of nerve cells, apparently creates these aggregates in mice. Animals genetically engineered to overproduce the protein also exhibit Parkinsonian symptoms. The team gave such mice monthly injections of their vaccine, and monitored the response. About half of the animals produced high levels of antibodies that fought the creation of Lewy bodies. “The vaccine helped to clear the alpha-synuclein from the brain,” Crews explains. After eight months of treatment, the older mice that received the vaccine showed a 47% decrease in alpha-synuclein protein compared with their control counterparts. The findings from the study appear in the journal Neuron. But researchers caution that the vaccine is far from a sure bet to battle Parkinson’s disease. “We don’t want to get ahead of ourselves. This requires more investigation,” says Crews.

Experts point out that the mice do not develop exactly the same condition that appears in humans, so it is hard to extrapolate to people. “The biggest challenges in developing vaccines for conditions like Parkinson’s disease include the availability of animal models that best reflect human disease,” says Howard Gendelman of the University of Nebraska Medical Center in Omaha, who is also working on a vaccine approach. Kieran Breen, director of research at the Parkinson’s Disease Society in London, also notes that the Lewy bodies’ role in the disorder remains unclear; preventing them from forming may not prevent illness. “It’s not known whether they are a cause or an effect,” he says.

July 5, 2005

Original web page at Nature