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September 18, 2004
Treating Disease by "Turning Off Genes"
Read more... Complementary Schizophrenia Treatments
Research has shown that many genes are involved in the epidemiology and symptomology of psychiatric disorders such as schizophrenia and bipolar disorder. Perhaps RNA interference molecule, currently being investigated for the treatment of macular degeneration, may one day be of use in treating these and other brain diseases.
This novel therapy, meant to turn off the abnormal or undesirable genes that cause certain diseases and symptoms, is set to be tested on patients suffering from macular degeneration.
The experimental treatment is an injection of RNA interference (RNAi) compound, which has been shown to turn off genes in a laboratory setting. There is no guarantee that it will have the same success in a human - similar molecules such as antisense and ribozymes have failed to be effective.
However, RNAi apparently has greater promise than any previously researched compounds; it seems to have more potent effects because it uses the cell's natural machinery. It is not a man-made chemical; it is a natural organic molecule originally discovered in worms in 1998. Some scientists think that this particular type of RNA may have evolved as a defense mechanism against viruses.
The molecular action of RNAi appears fairly straightforward. Although DNA (the building blocks of genes, which contain the essential codes for all proteins of the body) is double-stranded, RNA is normally single-stranded. One of its functions in the cell is to act as a "messenger" between the genetic DNA code and the cellular machinary that actually assembles the correct proteins. RNAi is able to bind to certain sequences of this messenger RNA, creating an abnormal "double-stranded" RNA molecule that the body recognizes as foreign and destroys. Thus, the information carried by that particular messenger about a certain protein molecule never reaches the building stage, and the protein is not produced. By disabling the link between the coding and the building phase of proteins, RNAi manages to "turn off" genes.
Theoretically, scientists might be able to synthesize sequences of RNAi that bind to and disable RNA messengers from certain disease-causing genes in the body.
Some preliminary animal tests with RNAi have proved effective. A research team at the University of Iowa used the treatment to improve ataxia (a hereditary brain disease that somewhat resemble's Huntington's) in mice.
Various pharmeceutical companies and research institutes are exploring the possibilities of using RNAi sequences to treat conditions such as hepatitis, diabetes, Huntington's, Parkinson's, and Lou Gehrig's disease.
One potential advantage of RNA treatment is that it makes multiple injections or medications unnecessary. If it can be very specifically targeted to just a few genes, it also has a very low potential for side effects. However, there may be certain drawbacks to such a gene-based therapy approach. RNAi might, for example, only partially repress a problem-causing gene rather than completely turning it off. It might also potentially target and reduce the action of other genes not involved in disease, causing unforeseen side effects. The body might also mount a major immune response against the double-stranded RNA molecules.
For the full story, see "Method to Turn Off Bad Genes Is Set for Tests on Human Eyes" (Sept 14, 2004). Source: The New York Times (http://www.nytimes.com).
Posted by Julia at September 18, 2004 04:33 AM
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