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.
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.