Fresh hope on brain disease

By Graeme O'Neill
October 16, 2005
A mouse makes its way through a special environment  designed to test brain activity, as part of the research at the Howard Florey Institute.

Photo: Michael Clayton-Jones

GROUNDBREAKING work on brain disease by Australian scientists has been hailed as a "revelation" in the treatment and prevention of degenerative brain disorders.

Neuroscientists have shown that the anti-depressant drug Prozac protects laboratory mice against the devastating hereditary brain disorder Huntington's disease.

The drug maintains normal brain function by stimulating nerve regeneration in the brains of the mice. Now, it is hoped that Prozac's protective and restorative powers could prevent Huntington's developing in humans.

Professor Perry Bartlett, director of the Queensland Brain Institute in Brisbane, described the finding as "a revelation on the road to Damascus" in the treatment and prevention of degenerative brain disorders.

He believes it will open the way to new therapies for other chronic neuro-degenerative disorders including Alzheimer's disease, Parkinson's disease and motor neurone disease.

Professor Bartlett is a co-author of a research paper, published this month in the European Journal of Neuroscience, which details the discovery.

The paper outlines how Prozac stimulates resident stem cells in mice to form new neurons that restore vital regions of the brain damaged by Huntington's.

Professor Bartlett said Huntington's was regarded as the most devastating and intractable of the chronic neuro-degenerative disorders and a classic example of genetic destiny.

"You couldn't find a more difficult model of a brain disorder and hope to repair or prevent it," he said.

"The most incredible thing is that not only did the mice maintain their motor skills, they retained their learning skills.

"This takes the research from being merely interesting, to indicating that the ability to make new nerve cells may be crucial to maintaining a healthy brain.

"If a devastating disease like Huntington's, which is genetically programmed, can be overcome by stimulating the brain's capacity to repair itself, we may be able to start addressing other chronic neuro-degenerative disorders like Alzheimer's and Parkinson's."

Huntington's patients suffer progressive, massive loss of neurons in the parts of the brain that mediate higher mental functions such as reason, decision-making and physical co-ordination.

A dominant-gene disorder, caused by mutations that lead to the production of proteins that kill neurons, Huntington's develops much earlier than other brain disorders — typically in middle age, but even in childhood — and its course is usually more rapid and severe.

A DNA test developed in 1993 can identify at-risk individuals in families with a history of Huntington's, and also predicts approximately the age of onset.

Because the disease is incurable, few members of Huntington's-affected families take the test, opting instead to live with uncertainty. Many decide not to have children.

The latest study builds on groundbreaking research by Australian neuroscientist Dr Anthony Hannan at Oxford University in 2000 and, more recently, at Melbourne's Howard Florey Institute for research.

At Oxford, Dr Hannan showed that regular exercise and a mentally stimulating environment dramatically slow the onset of chorea, the jerky movements seen in human Huntington's, and in transgenic mice with a toxic form of the human huntingtin gene.

Dr Hannan's group has recently shown that exercise and an enriched environment also protect the Huntington's mice against dementia and depression.

Enhanced physical exercise is known to alleviate depression, and Dr Hannan believes Prozac may replicate some of the beneficial effects of extra exercise and associated mental stimulation. Where sedentary, unstimulated Huntington's mice begin to exhibit symptoms from eight weeks of age and are severely affected by 16 weeks, the "enriched" mice performed normally in maze tests and were only slightly impaired physically.

Post-mortem analysis showed that specific regions of the brain normally affected by Huntington's were healthy and normal, with no shrinkage due to loss of neurons.

However, it would be much better and safer for people to exercise brain and body than to take the easy route and take drugs.

In 1992, Professor Bartlett, then at Melbourne's Walter and Eliza Hall Medical Research Institute, overturned decades of dogma when he discovered that the mammalian brain contains a self-renewing population of stem cells that give rise to new neurons. Previously, it was believed that neurons were not replaced during an individual's lifetime.
