June 19, 2007 A major obstacle in the treatment of infections and other diseases of the brain is the blood-brain barrier, which prevents systemically delivered therapeutic drugs from reaching the brain.
Grantees of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, have now shown that a short protein (peptide) from the rabies virus can carry a strip of therapeutic material into the brain via intravenous administration. Once delivered to the nerve cells of the brain, the strip, called a small interfering RNA (siRNA), was shown to protect mice from infection caused by the Japanese encephalitis virus (JEV).
Manjunath N. Swamy, M.D., of the CBR Institute for Biomedical Research and Harvard Medical School in Boston, and his colleagues used JEV to infect the brains of mice. They then injected the antiviral siRNA bound to the rabies peptide through the tail veins in one group of mice, while other mice served as control groups.
All the mice in the control groups died from JEV infection; in contrast, 80 percent of the mice that got the antiviral siRNA linked to the rabies peptide survived. These experiments demonstrate how the rabies peptide can be used to deliver antiviral siRNA across the blood-brain barrier and into nerve cells in the brain. Once inside brain nerve cells, the antiviral siRNA can silence key viral genes to control the infection. Furthermore, repeated administration of the RNA interference therapy did not trigger inflammation or antibodies to the peptide.
Currently, doctors use various methods to deliver therapeutic drugs directly into the brain. These methods involve invasive procedures that result in only localized delivery around the site of injection. The new research provides a safe and non-invasive method for delivering therapeutic molecules across the blood-brain barrier. It has the potential to be applied to the treatment of a variety of brain infections and diseases. The researchers are now trying to improve the efficacy of this delivery system and to make a stable form of siRNA that might yield even better results.
Article: "Transvascular delivery of small interfering RNA to the central nervous system," by N Manjunath et al. Nature DOI: 10.1038/nature05901 (2007)
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