Virus that came in from the cold: A dose of herpes could bring relief to Parkinson's disease sufferers. Ruth McKernan examines a radical treatment

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The Independent Online
Herpes is no longer a dirty word - at least not for sufferers of Parkinson's disease, who may one day be injected with the virus as part of a sophisticated new treatment for their disorder. Scientists are exploiting the once- feared microbe to develop what they hope will be a better method of restoring the chemical imbalance responsible for the symptoms of Parkinson's.

In this debilitating and painful disease, a specialised group of cells deep within the brain degenerates. Normally, these cells produce a chemical, dopamine, which transmits instructions from the brain to other nerves controlling movement of the limbs. But when the cells degenerate, levels of dopamine drop, causing tremors, feeble co-ordination and ultimately a frozen, statue-like posture - all features of Parkinson's disease. Although it is one of the most common ageing diseases, scientists still understand little about its cause.

Professor Peter Jenner, director of the Parkinson's Disease Society Experimental Research Laboratory at King's College London, says: 'With our current understanding it is more realistic to try to treat the symptoms than to try to prevent the disease.' To restore the levels of dopamine, doctors frequently prescribe a drug, L-Dopa, which is converted to active dopamine once inside the brain.

There are two drawbacks with this treatment. First, after long-term drug treatment it is difficult to maintain even levels of dopamine, which means unbearable swings in the activity of sufferers. Too little can stop patients in their tracks, like a child freezing in a game of 'musical statues'. Too much dopamine results in wild, uncontrollable and relentless movement. Second, as the disease progresses, the body's ability to convert L-Dopa to dopamine is lost: 'Within five to 10 years most patients will deteriorate so much that the drugs will stop working,' Professor Jenner says. The need is for a system to be developed that constantly delivers dopamine to the brain.

One controversial approach has been to take brain cells from aborted foetuses and transplant them into the brains of Parkinson's disease sufferers. Success has been limited and the procedure has problems. 'Six to eight fresh foetuses are required for each transplant and, even if the graft is successful, the underlying disease process could, itself, kill off the healthy transplanted cells,' Professor Jenner says. There is also the danger that if the foetal brain cells are not dissected precisely, cells that could develop into other types of tissue, such as skin or bone, could be accidentally dissected and transplanted.

The ethics of using foetal tissue for human transplantation are hotly disputed. The technique has been suspended in the United States. Scientists are continuing to research it and may still be able to overcome some of its shortcomings, but an alternative method of producing dopamine would be preferable.

Enter the herpes virus. Unlike most viruses, it can infect non-dividing cells, such as nerve cells. When active, it hijacks the host's cellular machinery to reproduce itself and then infect other cells, producing sores around the mouth or genitals as it does so. But the virus is inactive for much of its life, hiding out quietly inside nerve cells. In this form it doesn't multiply, produce any symptoms or cause any trouble.

Sufferers of 'cold sores' are all too familiar with the virus's habit of lying dormant for years and then bursting into blistering form just in time for that important social occasion. But it is just this 'hibernating' quality that makes it so useful. Scientists reasoned that if they could engineer the virus to make dopamine, it could act as a vector, carrying the genetic recipe for dopamine into the brain cells.

'We know a lot about herpes; it has the required properties and right now it is the obvious choice,' says the pioneer of the technology, Professor Alfred Geller, of the endocrinology group at the Children's Hospital in Boston.

The herpes virus is relatively simple. Unlike man, whose genetic blueprint is carried on 23 pairs of chromosomes, the herpes virus carries all its genetic information, 75 units or genes in total, on just one circular piece of DNA. Using the latest genetic techniques, Professor Geller's group has modified the circle of DNA. They have disarmed it by chopping out large chunks that carry instructions for reproduction, development and control of the infectious, harmful part of the virus's life cycle. Instead the scientists have inserted the blueprint for making the missing chemical, dopamine.

The genetically altered virus has been tested by injecting it into the brains of rats that have an experimental form of Parkinson's disease. Although herpes can usually travel through nerves, hopping from one cell to another when it reproduces, the 'tamed' virus cannot reproduce, so it must be injected just where it is needed.

Professor Geller's group has seen recovery in the rats. 'These experiments are still in progress, but we have reasonably good data that the virus is still working up to half a year later,' he says. Six months is a long time in the life of a rat, which normally lives only a few years, so the researchers are optimistic that the engineered virus would work in man for some time. If there is any truth in the saying that, unlike love, herpes lasts for ever, it could be a relief for sufferers of Parkinson's disease.

But the professor urges caution. 'We have established some important principles, but we are not going into the clinic,' he says. The system that looks so promising in rats could not be used in humans without further modification.

The problem lies in production of the engineered virus. Normally, geneticists can cut, paste and edit DNA and then grow unlimited stocks of the virus in a flask of cultured cells. The modified herpes virus will not grow in the laboratory. To make enough virus for their experiments, the group has devised a scheme where the instructions for reproduction and other vital functions are carried on a second, separate virus called a helper virus. Neither virus is complete and so neither can reproduce except under special conditions, allowing scientists to make their stocks.

'The principle that this kind of system works has been established, but the possibility of the two types of virus combining to produce a wild type of herpes means you could never use it in people. An improved version might be used in the future,' Professor Geller says.

British virologists are trying to develop a way of making the treatment safer. Instead of injecting a potentially fatal mixture of two viruses, David Latchman, Professor of Molecular Pathology at University College London Medical School, is trying to modify the herpes virus in a more specific manner. 'We want to develop a virus that will be able to grow in cultured cells, but would have specific defects on top that would prevent it from ever growing in the brain,' he said. They would then have only one type of virus, production would be straightforward and there would be no need to worry about lethal combination. Professor Latchman's team is trying to find out which factor or factors should be removed to produce the safest virus.

For Parkinson's disease, herpes therapy can offer only a treatment, not a cure, but scientists are optimistic they can improve and extend the technique to other diseases where the missing element has been established. 'In principle it is easy to deliver a protein to a small part of the brain. The technology favours diseases such as Parkinson's that affect only one specific region,' Professor Geller says.

The Nineties have been called 'Decade of the Brain' because of the rapid advances in scientists' understanding of the organ and its disorders. Professor Geller believes that by the end of the decade, Parkinson's disease sufferers could have cause to look forward to a dose of herpes.

(Photograph omitted)

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