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A Major Breakthrough in Gene Therapy
by Marsha Miller, Ph.D.

The Press Release

MINNEAPOLIS - For the first time, a dominant neurodegenerative disease has been successfully treated using gene therapy, according to a study presented today at the 7th Annual Meeting of the American Society of Gene Therapy (ASGT).

A research team led by Beverly Davidson, University of Iowa, investigated gene silencing by RNA interference (RNAi) as a potential therapy for Spinocerebella ataxia type 1 (SCA1), a dominant neurodegenerative disease caused by the expansion of the polyglutamine tract within the gene called ataxin-1. These are the same mechanisms underlying Huntington's disease, an inherited degenerative neuropsychiatric disorder which affects both body and mind.

Using RNAi expressed from within Adeno Associated Virus (AAV) vectors, researchers showed anatomical, pathological and functional protection from the inherited neurodegeneration in SCA1 transgenic animals. AAV vectors are present in many humans, but have never been associated with any disease, making them an excellent gene transfer vehicle.

The research provides hope for rapidly progressing towards a clinical trial for inherited dominant neurodegenerative diseases such as SCA1 and Huntington's disease.

HDAC Commentary

In 1998, an attendee at the HDSA national convention in Denver, Colorado asked a panel of researchers about gene therapy. The reply from one of the researchers was, "I won't say it will never be possible but right now it's science fiction. I can't imagine just how we'd go about 'snipping out' those extra CAG repeats." Just six short years later, gene therapy has become the most promising prospect for an eventual cure for Huntington's Disease and the focus has moved toward RNA interference. The idea is not to target the gene itself but the expression of the gene, to disrupt the instructions (the messenger RNA) to make the mutant Huntington's protein. The Hereditary Disease Foundation held a two day workshop in December 2002 to discuss this research.

http://www.hdfoundation.org/workshop/200212Report.htm

For those of us who sometimes wonder if progress is being made at all, reading the workshop notes makes it crystal clear that it has. Much discussion was devoted to the problem of the delivery system. Once there's a way to disrupt either the expression of the mutant gene or perhaps just those extra CAG repeats, how could doctors deliver this therapy to the neurons in the brain? Dr. Beverly Davidson discussed the difficulties of constructing an effective delivery system during this workshop and discussed the research her lab was doing to develop one. Just a year and a half later, she has done it. The specific research is with pinocerebella ataxia type 1 (SCA1), a disease very similar to Huntington's in that it is 1) caused by a dominant gene, 2) is a progressive neurodegenerative disease, and 3) is caused by the expansion of the polyglutamine tract.

To see a picture of Dr. Davidson and read more about her research, go to her web page: http://molbio.grad.uiowa.edu/faculty/FacultyDetail.asp?ID=8

Work remains to be done on the RNAi therapy for HD itself and then it will have to be tested in various mouse models before clinical tests could begin with people. It will take at least a few years, but this is progress for the HD community to be happy about. Gene therapy is no longer being called 'science fiction' and there's an effective delivery system when the therapy is ready.