Cystic Fibrosis and Gene Therapy
When studying for the final I became interested in finding out a little more about Cystic Fibrosis since we never had a student lecture over it.
Cystic fibrosis is a genetic disease that affects 30,000 children and adults in the United States. A defective gene causes the body to produce an abnormally thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. These thick secretions also obstruct the pancreas, preventing digestive enzymes from reaching the intestines to help break down and absorb food. The mucus also can block the bile duct in the liver, eventually causing permanent liver damage in approximately six percent of people with CF.
*We learned that this thick mucus is caused by the CFTR channels being mutated and therefore Cl- is not moved through the membrane.
More than 10 million Americans are unknowing, symptomless carriers of the defective CF gene. An individual must inherit two defective CF genes—one from each parent—to have CF. CF occurs in approximately one of every 3,500 live births. About 1,000 new cases of CF are diagnosed each year. More than 80 percent of patients are diagnosed by age three; however, nearly 10 percent of newly diagnosed cases are age 18 or older.
People with CF have a variety of symptoms including: very salty-tasting skin (*who tastes their own skin??); persistent coughing; wheezing or shortness of breath; an excessive appetite but poor weight gain; and greasy, bulky stools. Symptoms vary from person to person due to the excess of mutations of the CF gene.
The sweat test is the standard diagnostic test for CF. A sweat test should be performed at a CF Foundation-accredited care center where strict guidelines are followed to ensure accurate results. This simple and painless procedure measures the amount of salt in the sweat. A high salt level indicates CF.
The treatment of CF depends upon the stage of the disease and the organs involved. Clearing mucus from the lungs is an important part of the daily CF treatment regimen. Chest physical therapy is a form of airway clearance done by vigorous clapping on the back and chest to dislodge the thick mucus from the lungs. Other types of treatments include tobramycin solution for inhalation, an aerosolized antibiotic used to treat lung infections; Pulmozyme®, a mucus-thinning drug shown to reduce the number of lung infections and improve lung function; and azithromycin, an antibiotic recently proven to be effective in people with CF whose lungs are chronically infected with the common Pseudomonas aeruginosa bacteria. In addition, approximately 90 percent of all people with CF take pancreatic enzyme supplements to help them absorb food in digestion.
According to the CF Foundation's National Patient Registry, the median age of survival for a person with CF is in the mid-30s. As more advances have been made in the treatment of CF, the number of adults with CF has steadily grown. Today, nearly 40 percent of the CF population is age 18 and older. Adults, however, may experience additional health challenges including CF-related diabetes and osteoporosis. CF also can cause reproductive problems—more than 95 percent of men with CF are sterile. But, with new technologies, some are becoming fathers. Although many women with CF are able to conceive, limited lung function and other health factors may make it difficult to carry a child to term.
When scientists discovered the cystic fibrosis gene in 1989, they envisioned using normal genes as "drugs" to replace the defective genes to cure the disease. In theory, gene therapy corrects the basic, genetic defect that causes CF, rather than only treating the symptoms. Researchers must be able to add enough normal genes to CF airways to correct the defective cells with the goal of retaining existing lung function and preventing any further damage.
Researchers are developing innovative gene delivery systems to determine the best way to deposit healthy genes into the airways of people with CF. These "healthy" genes are manufactured in a laboratory using state-of-the-art biotechnology. Modified viruses that target the airways and compacted DNA are among the vectors being refined for potential gene transfer. Ideally, the healthy gene will be delivered via an inhaled aerosol or through a vein.
Recently, researchers have tested the safety of the adeno-associated virus delivery system, which is a method that is less likely to trigger the body's immune response than the adenovirus, another potential treatment. They are also monitoring patients to detect whether the normal CF gene has "turned on." If it has, the CF gene should produce a normal protein (the CFTR channel) that can transport ions across the cell membrane, a process that is vital to the health of cells lining the respiratory tract.
Another example of a possible gene delivery method is a unique compacted DNA technology, known as PLASmin™, which compresses individual molecules of DNA to their minimum size. The small size of these molecules facilitates the uptake of the DNA into the cell and into the nucleus without a virus or other vector to carry it. The unique capability of the PLASmin™ technology appears to be safe when tested in humans and could lead to a successful form of gene therapy for CF.
The first experimental dose of a gene therapy treatment was given to a person with CF in the spring of 1993.
A website that explained much of the information about Cystic Fibrosis was http://www.cff.org. Check it out.
Cystic fibrosis is a genetic disease that affects 30,000 children and adults in the United States. A defective gene causes the body to produce an abnormally thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. These thick secretions also obstruct the pancreas, preventing digestive enzymes from reaching the intestines to help break down and absorb food. The mucus also can block the bile duct in the liver, eventually causing permanent liver damage in approximately six percent of people with CF.
*We learned that this thick mucus is caused by the CFTR channels being mutated and therefore Cl- is not moved through the membrane.
More than 10 million Americans are unknowing, symptomless carriers of the defective CF gene. An individual must inherit two defective CF genes—one from each parent—to have CF. CF occurs in approximately one of every 3,500 live births. About 1,000 new cases of CF are diagnosed each year. More than 80 percent of patients are diagnosed by age three; however, nearly 10 percent of newly diagnosed cases are age 18 or older.
People with CF have a variety of symptoms including: very salty-tasting skin (*who tastes their own skin??); persistent coughing; wheezing or shortness of breath; an excessive appetite but poor weight gain; and greasy, bulky stools. Symptoms vary from person to person due to the excess of mutations of the CF gene.
The sweat test is the standard diagnostic test for CF. A sweat test should be performed at a CF Foundation-accredited care center where strict guidelines are followed to ensure accurate results. This simple and painless procedure measures the amount of salt in the sweat. A high salt level indicates CF.
The treatment of CF depends upon the stage of the disease and the organs involved. Clearing mucus from the lungs is an important part of the daily CF treatment regimen. Chest physical therapy is a form of airway clearance done by vigorous clapping on the back and chest to dislodge the thick mucus from the lungs. Other types of treatments include tobramycin solution for inhalation, an aerosolized antibiotic used to treat lung infections; Pulmozyme®, a mucus-thinning drug shown to reduce the number of lung infections and improve lung function; and azithromycin, an antibiotic recently proven to be effective in people with CF whose lungs are chronically infected with the common Pseudomonas aeruginosa bacteria. In addition, approximately 90 percent of all people with CF take pancreatic enzyme supplements to help them absorb food in digestion.
According to the CF Foundation's National Patient Registry, the median age of survival for a person with CF is in the mid-30s. As more advances have been made in the treatment of CF, the number of adults with CF has steadily grown. Today, nearly 40 percent of the CF population is age 18 and older. Adults, however, may experience additional health challenges including CF-related diabetes and osteoporosis. CF also can cause reproductive problems—more than 95 percent of men with CF are sterile. But, with new technologies, some are becoming fathers. Although many women with CF are able to conceive, limited lung function and other health factors may make it difficult to carry a child to term.
When scientists discovered the cystic fibrosis gene in 1989, they envisioned using normal genes as "drugs" to replace the defective genes to cure the disease. In theory, gene therapy corrects the basic, genetic defect that causes CF, rather than only treating the symptoms. Researchers must be able to add enough normal genes to CF airways to correct the defective cells with the goal of retaining existing lung function and preventing any further damage.
Researchers are developing innovative gene delivery systems to determine the best way to deposit healthy genes into the airways of people with CF. These "healthy" genes are manufactured in a laboratory using state-of-the-art biotechnology. Modified viruses that target the airways and compacted DNA are among the vectors being refined for potential gene transfer. Ideally, the healthy gene will be delivered via an inhaled aerosol or through a vein.
Recently, researchers have tested the safety of the adeno-associated virus delivery system, which is a method that is less likely to trigger the body's immune response than the adenovirus, another potential treatment. They are also monitoring patients to detect whether the normal CF gene has "turned on." If it has, the CF gene should produce a normal protein (the CFTR channel) that can transport ions across the cell membrane, a process that is vital to the health of cells lining the respiratory tract.
Another example of a possible gene delivery method is a unique compacted DNA technology, known as PLASmin™, which compresses individual molecules of DNA to their minimum size. The small size of these molecules facilitates the uptake of the DNA into the cell and into the nucleus without a virus or other vector to carry it. The unique capability of the PLASmin™ technology appears to be safe when tested in humans and could lead to a successful form of gene therapy for CF.
The first experimental dose of a gene therapy treatment was given to a person with CF in the spring of 1993.
A website that explained much of the information about Cystic Fibrosis was http://www.cff.org. Check it out.
posted by Robin at 2:42 PM
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