Tracing nervous reactions

Trinity researchers are studying chemical reactions in the body and how the drugs used to treat diseases such as Parkinson's …

Trinity researchers are studying chemical reactions in the body and how the drugs used to treat diseases such as Parkinson's interfere with them, writes Emma Napper

The human brain is the most complex network known to man. It contains around 10 billion nerve cells or neurones, which communicate with each other using a delicate balance of chemical messengers.

Prof Keith Tipton, head of neurochemistry in the biochemistry department of Trinity College Dublin, has dedicated much of his working life to understanding how these neurones and their chemicals interact, and to investigating what happens when the chemical balance is upset.

One of Tipton's main interests is the treatment of Parkinson's disease. Parkinson's patients often suffer from uncontrollable shaking and they gradually lose the fine-tuning that would normally allow them to change the speed of their movements or halt them.

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"Parkinson's disease is a progressive condition," says Tipton. "The first symptoms are tremors and then the patients get progressively worse. The body tries to over- compensate and then they get rigidity."

Although Parkinson's doesn't kill people, it can be debilitating. The disease has been brought into the spotlight by famous sufferers such as Muhammad Ali and Michael J. Fox. It affects 3,000 people in the Republic.

There are two types of neurone in the brain that control movement. One set of neurones says "do this"; the other set says "not so fast", explains Tipton. The "not so fast" neurones work by releasing a chemical called dopamine, which stops the "do this" nerves from firing. Another chemical, called mono amine oxidase (MAO), then comes along and mops up the spare dopamine swimming about between the nerves.

In Parkinson's, the "not so fast" neurones die at an alarming rate, and not enough dopamine is produced to keep the nerves that initiate movement in check. "We are all losing nerves all of the time," says Tipton. "The upper estimate is 750 nerves an hour, which is not too many considering how many we start out with."

However, by the time sufferers are diagnosed with Parkinson's, they may have lost as many as 80 per cent of their dopamine-producing nerves. Because the levels of MAO are still high, the levels of dopamine keep dropping and this causes a massive chemical imbalance in the brain.

One way to restore the balance is to give patients drugs that stop MAO mopping up what little dopamine is left in the brain. However, these MAO inhibitors have side-effects, the most common of which is the "cheese reaction", Tipton says.

MAO has a "part-time job" in the gut, working to digest certain types of foods. "These include cheese, red wine, avocado, broad beans and hedgehogs (which are eaten in some cultures)," says Tipton. Trying to inhibit the MAO in the brain can cause other serious side-effects elsewhere in the body.

These side-effects are important factors when designing drugs to combat diseases such as Parkinson's. Tipton and his group at Trinity have spent the last 10 years putting together a database of chemical reactions in the body, which will be able to show how altering the amount of one chemical will impact on other chemical pathways.

"You've got to know what you're doing," says Tipton "You need to know that by changing one pathway you aren't messing up another pathway. We are gathering more and more bits of the jigsaw puzzle and fitting it into a framework."

His final goal is to build a database that can be used by pharmaceutical companies to ensure that when a drug is designed to control one chemical reaction, they can predict the effect that it will have on all the chemical pathways in the body.

Emma Napper is a research scientist participating in the British Association for the Advancement of Science Media Fellow programme