Cystic fibrosis

Almost everyone has experienced the congestion that accompanies a bad cold. The thick mucus that forms in the nose and throat makes breathing difficult. Luckily, this congestion dissipates in a few days as the body fights off the cold.

However, individuals afflicted with cystic fibrosis must constantly cope withthe mucus which accumulates in the lungs, pancreas, and intestine. Cystic fibrosis, or mucoviscidosis, is an inherited disease that affects the exocrineglands. It is expressed only in the homozygous state without X chromosomal linkage. This genetic disease is often referred to as autosomal recessive. Thismeans that children born to parents who each carry one recessive gene for the disease have a 25% chance of inheriting both copies of the defective gene--and with them the disease. This common disorder mainly effects about 1 out ofevery 2,000 caucasians of European descent, and it is the leading fatal genetic disease in the United States. The disease is less common in African Americans and very rare in Asians and Native Americans.

Cystic fibrosis was not classified as a separate disease until 1938. In 1989,scientists at the University of Michigan and the Hospital for Sick Childrenin Toronto, Ontario, Canada, announced that they had identified the defectivegene that causes cystic fibrosis. The gene is found on chromosome 7, and over 600 mutations have been identified. Depending on the mutation, the symptomsand pathologies can range from mild to extremely severe. In 1992, scientistsat the Cystic Fibrosis Center at the University of North Carolina were ableto breed mice that showed human symptoms of cystic fibrosis. This newest achievement provided researchers with a model with which to study the disease.

Cystic fibrosis can be fatal if the mucus blocks the lungs. Patients may suffer from pneumonia caused by bacterial infections. Other serious complicationsinclude respiratory failure, diabetes, enlarged heart, liver cirrhosis, intestinal blockage, pancreatic disfunction, sodium deficiency, and sterility.

Abdominal cramps, malnutrition, growth retardation, and coughing are all symptoms associated with cystic fibrosis. However, the increased salinity of sweat is the most useful test to diagnose the disease. It is difficult to predictwhen any of these symptoms will appear or how severe they will be. While thedisease used to be fatal to nearly all children who developed it, more than50% of cystic fibrosis patients now live longer than thirty years.

Treatments are available for cystic fibrosis, but there is no cure. Often, antihistamines and decongestants are prescribed to open air passages. Cough suppressants are avoided since coughing helps to loosen the mucus in the tracheaand lungs. Antibiotics help to treat pneumonia, and studies of the over-the-counter anti-inflammatory drug ibuprofen indicate that it can slow pulmonarydecline. Physical therapy and surgery have also been used.

In 1990, researchers used laboratory cell cultures to correct the genetic defect that causes cystic fibrosis. They knew that the accumulation of mucus wascaused by a blockage of the cell channel used to regulate the flow of sodiumand chloride ions (Na+ and Cl-) in and out of the cell. The proper balance of these ions maintains the water balance of the mucusoutside the cell. This equilibrium is controlled by a specific protein produced by two copies of a single gene. If both genes are defective, cystic fibrosis occurs.

Scientists are currently investigating gene therapy as an approach to treating cystic fibrosis. The process involves inserting a copy of the normal cysticfibrosis gene into a virus that has been altered not to cause disease. The virus is then inserted into lung cells removed from a cystic fibrosis patient.Researchers have found that the normal gene reaches the DNA of the lung cells and begins producing the correct protein, leading to decreased mucus secretion. A unique approach to apply this technology to human use is the development of an aerosol spray. However, since viruses can cause problems in cystic fibrosis patients like inflamed lungs and swollen nostrils which make breathing more difficult, the spray approach uses liposomes (a sphere spontaneously formed when fat molecules are in solution) to act as the gene carrier, or vector. The liposomes are coated with the healthy cystic fibrosis genes and thensprayed in the nostrils. Scientists have found that some of the genes do makeit to cell nuclei in the lungs. Research continues into the effectiveness ofthis approach.

In 1996, scientists discovered that cystic fibrosis patients have a genetic defect that hinders the proper absorbtion of salt into lung epithelial cells.In turn, the resultant excess salt content inhibits a naturally occurring antimicrobial agent produced by these epithelial cells. With this natural defense system disabled, the immune system compensates by mounting a strong attackon bacteria. Unfortunately, this immune response is so overwhelming that it causes inflammation of the lung's minute branching airways, which further exacerbates the formation of mucus.

Rapid discoveries concerning the genetic factors in cystic fibrosis have ledto research into new therapeutic approaches. Researchers at the National Institutes of Health, for example, have developed a "gene-assist" drug called CPXthat helps promote chloride ion transport.With the development of new genetic testing technologies, physicians are able to test for a wider variety of the most common cystic fibrosis mutations known. As a result, a National Institutes of Health consensus panel has recommended that genetic testing should beoffered to couples expecting a baby or to become pregnant, especially if they have a family history of cystic fibrosis. Many scientific and ethical concerns are associated with genetic testing of cystic fibrosis. Genetic testing sensitivity for cystic fibrosis can vary greatly, which carries the risk of not identifying a carrier or fetus with the disease. In addition, genetic counseling should be offered to couples at risk, but there is a shortage ofgenetic counselors. Finally, information about a person's genetic predisposition to cystic fibrosis and other diseases could lead to discrimination by employers and insurance companies.

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