Towards gene therapy for tobacco-related vascular disease
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Users of tobacco products frequently develop diseases of their blood vessels, leading to complications such as heart attacks, difficulty walking, strokes, and death. Unfortunately, many of the treatments for blood vessel disease are less effective in smokers than in nonsmokers. These treatments include surgery to rebuild, bypass, or enlarge blocked blood vessels. The disappointing results that are associated with these procedures when they are performed in tobacco users have even caused some physicians to refuse to provide such treatments to patients who continue to smoke. Even when these patients can be convinced to quit using tobacco, their increased risk of developing complications of vascular disease continues for up to 2 years. For these reasons, new therapies for blood vessel disease are required that are effective in smokers and in recent ex-smokers.
 
 
 
 
 
 Examination of the characteristics of blood in tobacco users has provided clues as to why tobacco users are at higher risk for developing complications of blood vessel disease and are less responsive to surgical procedures performed on blood vessels. Smokers' blood clots more easily than that of nonsmokers, and many of the more serious and fatal complications of vascular disease (listed above) are caused by abnormal clotting that results in blockage of critical blood vessels. In addition, many of the same proteins that cause blood to clot appear to cause blood vessels to develop abnormal growth, resulting in narrowing and eventually closure. It is possible that a therapy that counteracted the effects of these proteins both on the blood vessel wall and on blood that comes in contact with the vessel wall would be effective in treating tobacco related vascular disease. For example, if such a treatment were administered to the blood vessel wall at the time of a surgical procedure, then this procedure might be as effective in smokers as in nonsmokers.
 
 
 
 
 
 To begin to develop a local treatment that would improve the results of blood vessel surgery in smokers, we have identified two proteins that may be involved in protecting blood vessels from tobacco related disease. Our goal is to develop a gene based therapy in which the gene that encodes one of these proteins is inserted into the cells of the blood vessel wall. Once the gene is introduced into these cells, the blood vessel itself will become a type of "factory" that manufactures the protein locally and protects itself from the harmful effects of tobacco use. We have developed efficient techniques for transferring these two genes into blood vessel cells. Before we are ready to apply this therapy in humans, however, we must test it in animal models of blood vessel disease. These experiments will tell us what exactly is the effect of introducing these genes into the blood vessel wall. We will test whether introduction of the genes makes blood vessel disease worse or better in the animals If either of the genes is effective in preventing blood vessel disease in the animals, in the future we will attempt to develop safe techniques for introduction of the gene into human blood vessels. Our eventual goal is to use this "gene therapy" to improve the results of blood vessel surgery We anticipate that this therapy will be particularly helpful in improving the results of blood vessel surgery carried out in smokers.