Gene study gives hope to victims of Parkinson?s diseases

The prospect of treating inherited diseases by switching off defective genes, leaving healthy genes unharmed, has come a step closer, a study showed yesterday. Incurable illnesses such as Huntington's disease and other disorders of the brain and nervous system could eventually be treated by the technique, the scientists involved in the research say.

The researchers have demonstrated the treatment, using the revolutionary process of RNA interference. RNAi has become the hottest topic in medical science since scientists showed last year that it can destroy damaged or defective genes in human cells almost at will.

Last December, RNAi was voted "breakthrough of the year" by the journal Science, four months after The Independent highlighted its importance in a series of articles. The latest research was done on genetically defective human cells in a test tube. The scientists believe the findings are a powerful demonstration that RNAi could also be used on real patients suffering any of the many thousands of inherited disorders.

Henry Paulson, of the University of Iowa, who led the research, said the study was aimed at seeing whether RNAi was powerful enough to turn off diseased genes even when they were "dominant", meaning that inheriting just one defective copy from a parent always resulted in the illness.

"Many labs have used RNAi to knock down expression of a gene," Professor Paulson said. "We asked the question, can we apply this to dominantly inherited diseases? Many inherited neurological diseases are due to dominantly acting mutations that produce toxic proteins. We targeted disease genes while sparing the normal copies of the gene. [It] shows you can eliminate expression of the bad gene while maintaining the activity of the good copy."

The research, published in the journal Proceedings of the National Academy of Sciences, investigated RNAi's gene-silencing power on human cells affected by mutations causing Machado-Joseph disease, an illness of the brain and spinal cord, and a genetic form of Parkinson's disease.

"Many human diseases, in particular the inherited neurological diseases I see in my clinic, are untreatable and devastating disorders," the professor said. "Patients and their families are desperate for something that can slow or stop it.

"This is true for the [two] diseases we targeted. Huntington's is another example. In the prime of life, affected persons with Huntington's develop problems thinking, controlling movements and harnessing their emotions. Although we can treat some of the symptoms in these diseases, we cannot slow their relentless progression."

Scientists did not understand precisely how any of those toxic disease genes caused brain cells to become sick and die, Professor Paulson added. "But it seems clear that eliminating the toxic gene product - the bad protein - would be ideal. If we or others can develop this technology into a therapy that silences toxic disease genes in humans, it would have a huge impact for patients and their families."

The research also shows how precise the RNAi technique is. It distinguished between the healthy and diseased version of the same gene, though they differed by only a single change in the DNA sequence of chemical bases or "letters".

"If researchers can come up with efficient ways to deliver RNAi to specific organs in humans, RNAi's potential as a therapeutic agent for acquired and genetic diseases is vast," the professor said.