Cold sore virus possibly could help treat Parkinson's disease

London 10 January 2000Innovative treatments using viruses to deliver gene therapy are proving successful in experimental systems, and could one day be used to help patients with Parkinson's disease. The pioneering research is reported in the November 1999

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Journal of the Royal Society of Medicine by Dr. David Latchman, who is attached as a Professor of Human Genetics at the Institute of Child Health in London.

In gene therapy, genetic information is introduced into the body of the patient to treat disease. For example, Parkinson's disease results from a loss of dopaminergic neurons. These are the nerve cells which produce the hormone dopamine. One approach to treatment is to try and slow down or stop the death of these neurons. The most safe and effective way of delivering treatment for this is by delivering the gene which encodes GDNF, known as the glial-derived neurotrophic factor, a substance which helps these neurons survive.

Another approach consists in increasing the body's supply of dopamine by introducing proteins like tyrosine hydroxylase, which help to largely enhance dopamine production. If these proteins are placed directly into the body, the body's cells cannot access it. Instead, the protein has to be delivered to the nervous system in a genetically modified dopamine-producing cell, or as a tyrosine hydroxylase gene itself.

One of the most effective ways of getting genetic material into the body is to use viruses. Professor Latchman points out that viruses have evolved over millions of years to introduce their DNA into the human cells with extremely high efficiency, and that researchers can exploit this capacity by using them to deliver foreign genes. One of the best is herpes simplex (HSV), the virus which produces cold sores. It can deliver genes for tyrosine hydroxylase or GDNF straight to the brain.

The herpes virus is easy to grow in a laboratory, and since it is bigger than most viruses, the geneticist can remove some of the virus' own genes and replace them with all the "foreign" genetic material the patient needs. HSV is also good for delivering material to the nervous system since during its life cycle, it naturally settles in neuronal cells, where it is free of symptoms.

The "normal" virus will use these cells as a base from which to replicate. This causes the herpes infection that we see and feel in cold sores, genital sores, and more seriously, in lethal encephalitis. If a virus is being used to deliver treatment, it must be disabled so that it won't start to cause its "usual" disease. This can be achieved by separating out the genes that tell the virus to start replicating, and supplying them only in the cells used to grow the virus.

Professor Latchman's laboratory has managed to use the disabled, modified virus to treat Parkinson's disease in experimental model systems. Of course, more research needs to be done to find the best combination of therapeutic genes and the safest way of disabling the viruses used, but it is a very real possibility that this method will eventually be a big step forward in treating Parkinson's, especially where drug therapy has failed.

You can find more details on gene therapy in the current VMW issue in the article Researchers to prepare "gene tonic" for the extinguishing brain of Alzheimer's patients.


Leslie Versweyveld

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