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SAN DIEGO, Monday, July 25, 2005 – A team of researchers, led by Roger Davis of the San Diego State University Heart Institute, has executed a war plan from Greek mythology to help grab the upper hand in the fight against heart disease.

In lab experiments using mice genetically altered to reflect a severe and sometimes fatal form of heart disease called homozygous hypercholesterolemia, Davis and his colleagues used bone marrow stem cells as “Trojan horses” to carry a synthetic, therapeutic gene into the liver. This enabled the synthetic gene to prevent narrowing of the arteries, known as atherosclerotic lesions, by 50 percent.

“All of the mice we tested appeared healthy and none showed any unwanted side effects,” Davis said of the results, which appear today in the journal Proceeding of the National Academy of Science. “Additionally, it looks very promising that the technique can be further developed for use in humans to treat several deficiency diseases and to enhance the ability to vaccinate individuals for preventing and treating cancer and infectious diseases.”

Enthusiasm to apply gene therapy for treating human disease was common within the biomedical research community in the 1980s because of selectivity of specific genes to cure many types of diseases.

“People had great expectations for gene therapies, but the major barrier over the years has been to deliver a gene to a tissue target without causing unacceptable side effects,” Davis said. “Our novel gene therapy is likely to provide a major breakthrough to safely apply gene therapies for human use because we avoid the direct administration of virus to the patient by using easily obtained stem cells as a vehicle to deliver the therapeutic gene to the liver in the form of replaceable (liver) macrophages.”

The technique requires an intravenous injection of gadolinium chloride, the same non-toxic chemical used in medical tests to visualize human coronary arteries. The chemical triggers a reaction that causes existing liver macrophages to be removed and replaced by new ones derived from the “Trojan horse” stem cells bearing the therapeutic gene.

Supported by an eight-year grant from the National Institutes of Health, Davis brought together researchers from San Diego State, The Scripps Research Institute and the University of California, San Diego. While Davis planned and directed the research, Linda Curtiss, a Scripps immunologist, characterized the stem cells and measured atherosclerosis lesions and Christopher Glass, a UCSD molecular geneticist, provided expertise for the construction of the synthetic therapeutic gene allowing selective macrophage expression. Additional team members from all three institutions included undergraduate and graduate students and junior faculty.

Davis indicated that the next step is to modify the experiment to test its ability in mice to treat genetic deficiencies such as Gaucher disease, Tay-Sachs disease and hemophilia, and to provide immune therapy against specific cancers.

“Our encouraging results both reflect the success of academic research funding by the NIH and are consistent with our goal to have safe and effective gene therapies available for testing in humans in two to three years,” he said.

Later this year, Davis will be the first researcher to move into the SDSU Bioscience Center, a new 38,000-square-foot laboratory and classroom facility dedicated to investigating the links between and treatments for cardiovascular and infectious diseases.

San Diego State University is the oldest and largest institution of higher education in the San Diego region. Founded in 1897, SDSU offers bachelor's degrees in 81 areas, master's degrees in 72 and doctorates in 16. SDSU's nearly 33,000 students participate in academic curricula distinguished by direct contact with faculty and an increasing international emphasis that prepares students for a global future. For more information log on to www.sdsu.edu.

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