Cystic Fibrosis Essay, Research Paper

Caucasian people carries at least one of the fatal defective genes that cause

cystic fibrosis, CF, or mucoviscidosis (in Europe) although carriers don’t show

any signs of the disease. Therefore, 10 million2 people carry the defective gene

and aren’t aware of it. Consequently, it makes it one of the most common genetic

defect in the United States. CF is a autosomal recessive gene. That means that

it may, but doesn’t always skip generations. In order to get this disease, both

parents must be carriers. If one parent has CF and the other one is not a

carrier than there is a 100% chance that their child will be a carrier. If one

parent has CF and the other is a carrier than the child has a 50% chance of

having CF and a 50% chance of just being a carrier. If both parents are carriers

than their child will have a 25% of having CF, a 50% chance of being a carrier

and a 25% chance of not being affected. CF is common in both males and females,

there is not a specific sex that it is more common in. How does a person know if

they have CF? There are many symptoms to this deadly disease including: salty

tasting skin, constant coughing, large amounts of mucus, trouble gaining weight,

frequent greasy, foul smelling bowel, growths in the nose (nasal polyps) and

clubbed or enlarged fingertips and toe tips is another symptom. Now there are

many tests that can be done to find put if a person has CF. One way which CF can

be detected is to observe the symptoms. A person doesn’t need to have all the

symptoms in order to have cystic fibrosis, but they usually show most of them.

Another way are different genetic testing. Doctors can now do genetic testing

for CF, but about 10 years ago they couldn’t. In 1989, the location where the of

the defective gene on chromosome number 7 is was discovered by Francis S.

Collins from University of Michigan. Tests can now be taken to see if an unborn

child is infected with CF such tests are amniocentesis, chronic villus biopsy3

and a removal of cells from the embryo during invitro. Many years ago, New York4

had a heat wave, and the hospitals became overwhelmed with dehydrated CF

children. These children became dehydrated much quicker than children without

the disorder. Thus eventually resulting in the formation of the sweat test which

is now the standard test. Doctors place a pad or filter paper on a patients arm

or back. A chemical called Pilocarpine, makes a burst of electricity to produce

more sweat. Then the pad is wrapped in plastic and is sent to a lab to get

analyzed. The doctors then would look for a high chloride content in the sweat.

Another test is a blood test that is administered 3 days after a baby is born.

It is called Immunoreactive Trypsinogen5 if that comes back positive it is then

double checked with a sweat test. Furthermore CF causes the sweat glands to

release about 5 times6 as much salt as a normal person would. This is why the

skin of a CF patients may taste salty. They don’t sweat more, but when they

perspire more salt is excreted. This causes the person to dehydrate. CF is a

disorder that causes the body to produce larger amount of mucus than normal. In

a normal person, mucus in the lungs helps get rid of germs and bacteria in the

air. In a CF patients the lungs become covered with a sticky mucus that is hard

to remove and promotes infection from bacteria. Over time infections cause the

lungs to become extremely weak, therefore ending in respiratory failure. Also CF

affects the digestive tract. The overproduction of mucus causes the pancreatic

ducts to be clogged. Therefore preventing necessary enzymes to digest fats and

proteins. Without those enzymes CF patients can’t gain weight. The undigested

proteins and fats pass right through the body creating smelly bowel. In some

cases this malnutrition causes people to die when they are only children. Also

it is more common for people with cystic fibrosis to develop digestive tract

cancer7. High levels of the protein CFTR (which the gene makes) are found in the

digestive tissues. Doctors explain this increased risk of cancer because CF

induces change in the digestive tract organs that causes the cell turnover.

Patients with gastrointestinal tract problem should get examined for such

tumors. Women with CF can have children, but it is not very common. Giving birth

is a vigorous process and puts the mother’s health at risk. It may also be hard

for a women to get pregnant though because the mucus blocks the sperm from

entering the uterus the to the fallopian tubes. About 98% of men with CF are

infertile8. Even though sperm are produced, they can’t get to the semen because

the vas deferens is blocked. In some new research, it has been thought that men

who are sterile have a different form of CF that doesn’t involve the digestive

system and the lungs. There are now many drugs that are in the market and many

more that are in development. Treatments mainly depends on what organs are

effected. The first new drug therapy in 30 years was approved by the Food and

Drug Administration in December of 93′. It’s a mucus-thinning drug called

Pulmozyme?. Pulmozyme? has reduced the number of respiratory infections and

improved lung function. There is also postural drainage or thumps. This

treatment is when the patient is hit on the back and chest with cupped hands to

loosen the mucus so it can be coughed up easier. There are many antibiotics that

help treat lung infections. Also medicated vapors are inhaled and open clogged

airways. Since mucus in the intestines causes the food not to get digested,

there are enzyme supplements to help. Those enzymes allow patients to go back to

a normal diet. Due to the high concentration of the enzymes the end result is

deterioration of the pancreas leading to diabetes. With the supplements CF

patients can eat normal food. There are now many studies that the medicine

ibuprofen (Advil, Motrin IB, Nuprin) prevents serious damage to lungs in

children who have CF. The trials involved 85 patients between the ages of 5 and

39 with FEV1 equal or greater than 60%9. In this study patients that took

ibuprofen had a slower rate of decline of FEV1. Patients that took it for 4

years consistently had even better results and showed best in patients under the

age of 13. The dose of ibuprofen was selected between 50 and 100up/mL because

the anti-neutrophil effects of ibuprofen are only attained at these levels.

There are some side effects, including conjunctivitis (unknown reason) and

epistaxi (due to the anti-platelet action in the ibuprofen. Doctors say that it

is not sure if stomach pains are due to the ibuprofen, but to stay on the

medicine and to take antacids with magnesium and aluminum and not those

containing calcium. In 1990 two teams of researchers were able to correct CF

cells in a petri dish10. The next huge step happened in 199311, when the first

experimental dose of gene therapy was administered to a human. These were

milestones in finding a cure or a preventive treatment. They were huge steps

because it marked the first time that scientists were able to test new

technology in people with the disease. Also in October of 93′12 scientists at

the University of Iowa made another big step, they determined that the CF gene

treatment worked! It had repaired the defective CF cells. This too was the first

time that the basic defect was corrected in people with the disease. Doctors and

scientists know that the gene number 7 is the gene that CF is found upon. They

also know that gene’s protein product most likely induces the movement of

chloride directly or indirectly. They named the protein ,cystic fibrosis

transmembrane conductance regulator (CFTR). While scientists and doctors were

looking for the gene, they also discovered that there is an abnormality in the

DNA of 70%13 of cystic fibrosis cases. That abnormality often called AF508

mutation, is made of the deleting of 3 nucleotides from that gene, that then

causes the protein product to be missing an amino acid named phenylalanine at

position 508. Doctors are now trying to get to this gene mutation and fix it.

Scientists are trying to think of a way to administer healthy CFTR genes to the

patients through gene therapy. If all goes as planed the DNA injected will help

the cells to make the normal CFTR protein and cystic fibrosis will then be

terminated. Doctors have many "delivery vans" that deliver the good

genes. Doctors transport them in viruses, fat capsules and synthetic vectors14.

They are put in the body through the nose or bronchial tubes. Nine human gene

therapy research studies are in the works as of now. Six of these nine are using

the "delivery vans" to deliver healthy genes to the lungs or the nose.

In one study the patients are given repeated doses of the CF gene therapy

treatment to the lungs. While other studies gives repeated doses of the gene

therapy to the nasal tissue of the patients. The other studies are using the fat

capsules for delivery, another is making the fat capsule in air form and are

breathed in by the patients. Putting the good genes in AAV (adeno-associated

virus) is another way of getting the genes in the body. In the last study, are

also uses the AAV to get the healthy genes into the lungs. There are about

ninety people with CF who have gone through some sort of gene therapy.

"There is a long way still to go before we have a cure for cystic fibrosis,

but we are moving in the right direction," says David Porteous of the

Medical Research Council’s Human Genetics Units at Edinburgh University.

Recently a grant15 has just been given to a company named Aradigm that might get

us closer to a better delivery vector. Dr. Igor Gonda, Aradigm’s Vice President

of research and development says, "By combining gene therapy with the AERx

delivery system, our research could ultimately lead to a broadly-applicable

technology for delivery of genes and olignucleotides to the respiratory tract.

Diseases which might be treated by such genetic therapies include respiratory

infections, lung cancer, emphysema, asthma and cystic fibrosis."16 Cystic

fibrosis is a genetic disorder that affects not only it’s victims, but it’s

victims family and friends. Thanks to modern medicine and new techniques, the

median survival rate has gone from 8 years old in 50’s to 30 years old in the

late 90’s17. Unfortunately, all this new medication and discoveries has come to

late for many people. One such individual is Alex Deford. She died when she was

only 8 years old. Her father, Frank, wrote a book based on her life and their

many struggles, from ignorant doctors who wouldn’t believe a dying child about a

collapsed lung and the disease itself. Many times with any genetic disorder, the

parents blame themselves. After all it was their bad genes that caused it.

Actually, when Alex first went into the hospital to get a sweat test, it came

back negative, when in reality it was positive. That was back in the early 70’s

though. Now sweat tests have few oversights. Cystic fibrosis is a disease that

doesn’t take any prisoners. All victims will eventually die from complication

due to CF. There are approximately 30,00018 children and adults that are living

with this disorder. Now that scientists have found the gene in which CF is

located, new medicines and new therapies will hopefully be invented. Perhaps in

the next century, we can say that cystic fibrosis is completely abolished. Maybe

the new medications and therapies won’t have to be as painful as they are now.

Why should these individuals with CF be made to suffer in order to get better.

Frank Deford says about chest physiotherapy and the disease, "Two thousands

times I had to beat my sick child, make her cry and plead…and in the end for

what?"

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