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Preeti Bhat
Dr. LeFebvre and Mr. Derek Dockter
UCD; Cluster Seven; Biomedical Sciences
Diseases Treated by Gene Therapy
Abstract
Gene therapy proves to be both extremely useful and successful when it comes to
the treatment of several diseases. Gene therapy also has the ability to target both
inherited and developed diseases and disorders. Among these diseases and
disorders are Haemophilia, Adenosine Deaminase Deficiency, Cancer, and
Parkinson’s. Gene therapy has either proven that it is effective in curing these
diseases or is headed on the right path in doing so.
The recent discovery of gene therapy has shaken up those in the medical field. Genes are
recognized as the basic biological code. The novel idea of gene therapy was brought up in the
1970s when scientists came up with the idea to perform “gene surgery” to fix a defective gene.
However, it wasn’t until the 1990s when scientists and researchers started to take gene therapy
seriously and make headway. Today, due to the potential of gene therapy, it is used to cure wide
varieties of diseases and disorders. Among these diseases are not only inherited diseases like
Haemophilia and Adenosine Deaminase Deficiency, but also developed diseases like Cancer and
Parkinson’s disease.
One of the most common inherited diseases that can be treated by gene therapy is
haemophilia. Haemophilia is a genetic disorder where an individual is unable to properly clot
their blood. As soon as a person is wounded, blood should begin clotting through a process
utilizing proteins called clotting factors. However, for those who have hemophilia certain
clotting factors have mutations. (Who Am I?). Haemophilia takes on three varieties, Haemophilia
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A, B, and C. Individuals with Haemophilia A have a deficiency of clotting factor eight while
those who have Haemophilia B have a lack of clotting factor nine. Then there are individuals
who suffer from Haemophilia C and they do not have enough of clotting factor eleven (About
Bleeding Disorders). This disorder is seen only on the X chromosome, making males the main
recipient of the disease while females take on the role as carriers. Any individual who is affected
by haemophilia usually experiences prolonged bleeding, internal bleeding, and bruising. Today
most individuals with the disorder prefer to be injected with clotting factors derived from blood
donors; this method has been used since the 1970s (Who Am I?). Recently, researchers have
developed another method of treating this disorder with gene therapy. A common gene therapy
procedure in curing all classes of haemophilia is when scientists remove a cell containing the
defective gene, typically from the liver, where the clotting factors are produced. Later, they
modify the cell by inserting genetic material which reprograms the cell to produce the missing
clotting factors. Finally, they reinsert the cell into the patient. After the gene therapy has been
performed, the cell is able to effectively survive and reproduce therefore curing the patient of
their haemophilia. This method has been in use since the 1990s, and so far, the success rates have
been growing with both humans and animals. In fact an entire colony of dogs in Chapel Hill,
North Carolina were cured of their haemophilia using this approach (Cure for Haemophilia).
Another method that has been proven effective, particularly for Haemophilia B, had recently
been published by The New England Journal of Medicine in 2011. Scientists used a modified
virus called adenovirus – associated virus 8, which carried double stranded DNA that coded for
the normal production of clotting factor nine, and injected it into six men with Haemophilia B.
All of these men had less than 1% of the clotting factor when they started with the injection, but
within 6 – 16 months of the study, their levels of the clotting factors increased anywhere from 2-
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11%. At the end of the study four of the six men were able to stop taking regular clotting factor
injections, and none of the patients had developed an immune response to the treatment
(Adenovirus-Associated Virus Vector-Mediated Gene Transfer in Haemophilia B). Ultimately,
researchers believe that gene therapy is not only an effective approach of going about treating
this disorder, but also proves to be more economical. According to Dr. Katherine P. Ponder of
Washington University School of Medicine in St. Louis, the cost of regular injections of clotting
factors per year costs is about $30,000. Thus, for an entire lifetime, it costs about $20 million,
and when compared to a single treatment of gene therapy a patient would spend only about
$30,000 (Wade, Nicholas).
The second most common inherited disease that can be treated by gene therapy is called
Adenosine Deaminase Deficiency (ADA) or “bubble boy disease”. The disease damages the
immune system and causes severe combined immunodeficiency (SCID). Those who suffer from
this disease have little to no protection from bacteria, fungi, and viruses. Their weakened
immune system are more susceptible to infections, and those infections seem to always be long
lasting (Adenosine Deaminase Deficiency). The cause of the disease is a mutation in a gene on
chromosome 20, the gene codes for the enzyme ADA. Without the enzyme, the molecule
Deoxyadenosine builds up and ends up destroying infection-fighting immune cells called T and
B lymphocytes (Adenosine Deaminase (ADA) Deficiency). The common symptoms of this
disease include chronic diarrhea, skin rashes, increased susceptibility to infections, and
complications of development during childhood (Adenosine Deaminase Deficiency). A majority
of patients who have ADA-SCID tend to go through bone marrow transplants, transfusions of
red blood cells, or enzyme replacement therapy as their treatment options (Adenosine Deaminase
(ADA) Deficiency). Gene therapy is another significant method of treating ADA. Even though
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the most successful cure for ADA through gene therapy was found recently, a cure not as
successful as the current one had been discovered. Previously gene therapy was used in the
1990s to treat a four year old girl with ADA, but due to ethical issues, she was mandated to go
back to her usual enzyme injections, and the therapy wore off in a matter of years. It wasn’t until
2002 that the topic of ADA and gene therapy had resurfaced and then later in 2009 was the
ultimate cure for ADA discovered (Public Health Genetics Unit). Recently, The New England
Journal of Medicine published a study regarding gene therapy and its ability to cure patients who
had ADA. During the study researchers removed a sample of marrow cells from each of the
patients and inserted the cells with working copies of the gene. Eventually, they performed an
autograft. The cells were able to survive and thrive (Gene Therapy Cures Fatal Bubble Boy
Disease). Overall, at the end of the study, eight out of the ten patients who were part of the study
were able to discontinue their required enzyme replacement therapy (Gene Therapy for
Immunodeficiency Due to Adenosine Deaminase Deficiency). Although gene therapy is effective
in the context of inherited diseases, this approach also does well when treating disorders that
develop during a human’s lifetime.
Cancer is an extremely common disease that is developed during one’s lifetime. A very
basic definition of cancer is when cells in the body divide uncontrollably forming a tumor (What
is Cancer?). These abnormal cells lack a growing mechanism called contact inhibition. This
means that on a normal basis, cells will reproduce in single layers but will stop when they come
in contact with other cells. This signals that there is not enough free room available to grow.
However, in the case of cancer cells there is no concept of contact inhibition and thus cells will
build up on each other creating tumors (Contact Inhibition). Depending on the type of cancer the
tumor can be benign, meaning that a tumor forms but will not spread and can be easily removed
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through surgery. On the other hand, there are malignant tumors which are the cause of millions
of deaths around the world each year. This form of cancer is able to spread throughout the body
using the blood and lymph systems. (What is cancer?). Today patients with cancer must first go
through surgery to remove most or all of the tumor and then go through the experience of both
chemotherapy and radiation. Because there are several varieties of cancer, gene therapy
treatments vary depending on the type. The two most common forms of gene therapy used in
treating cancer is replacing a defective gene with an effective gene within cancerous cells and
silencing a mutated gene by modifying it genetically. The first from of gene therapy has to do
with the mutated p53 protein found on cancer cells, this defect doesn’t allow for the cell to go
through apoptosis, which is cell death. However, this approach ensures that a normal p53 protein
is introduced into the cell. The result is an increase in sensitivity towards chemotherapy and
radiation unlike normal tumors. Additionally, in some instances, the therapy will allow for
apoptosis to take place. The second gene therapy treatment is called gene silencing. Gene
silencing occurs when a mutated gene is modified so it inhibits the expression of a specific gene
that causes tumors to grow. The genes that are blocked are called oncogenes, they code for the
constant cell division that makes cancer so deadly (Cancer Gene Therapy and Cell Therapy).
Although, several forms of gene therapy have been developed, the success rates aren’t as high as
researchers and scientists hope. However, a recent study was published in the journal Science
Translational Medicine where a form of gene therapy proved to be quite successful. Five
patients, whose cancer was deemed untreatable, were injected with genetic material into their
white blood cells. Later, the modified white blood cells turned into cancer fighters and were able
to destroy all cancer cells, eventually allowing the patients to go into remission (Clark, Daniel).
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Even though the success rate for gene therapy when it comes to cancer is slim, there is definite
potential in it.
Another developed disease that is treated by gene therapy is a neurodegenerative disease
called Parkinson’s disease. The disease is caused due to the death of dopaminergic cells in the
substantia nigra of the brain (NINDS Parkinson’s Disease Information Page). Dopamine is a
neurotransmitter, which is a chemical messenger that helps in sending signals to other parts of
the brain as well as other areas of the body (Mandal, Ananya). Individuals with the disease will
typically have tremors of the hands, arms, legs, jaw, and face. They might also experience
stiffness in their lower body and slow movement (NINDS Parkinson’s Disease Information
Page). Unfortunately, both researchers and scientists have not yet been able to find the cause
behind the disease nor a permanent treatment (What Causes Parkinson’s Disease?). At the
moment, people who have Parkinson’s take medications like levodopa in conjunction with
carbidopa. The two medications working together help produce and replenish the supply of
dopamine within the brain. With that said, there is still a downside to the drugs. For instance,
taking the medication doesn’t cure all symptoms of the disease, and one must continuously use
the medication for any alleviation. The patient also has the choice to go through a therapy called
deep brain stimulation (DBS). This approach calls for the careful implantation of electrodes
connected to a pulse generator in the brain. The treatment reduces the amount of medication
needed and lowers the amount of tremors one might have (NINDS Parkinson’s Disease
Information Page). Yet, there is still an alternative method to going about stopping the disease in
its tracks and possibly reversing the symptoms, this method of course is called gene therapy.
Researchers at Northeastern University in Boston have been able to plant nanoparticles nasally.
These particles carry a gene that is able to save dying neurons within the brain. The only
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downside to this study is that it has not been approved for clinical trials yet. (A Noninvasive
Avenue for Parkinson's Disease Gene Therapy). Hopefully, gene therapy and research will make
significant progress so that in the future there will be a cure for Parkinson’s.
From the 1970s to the 21st century, gene therapy has certainly progressed and advanced.
It seems as each day comes there are more discoveries and developments revolved around gene
therapy and its ability to cure several diseases. In fact, as of July 17, 2013 researchers at the
University of Massachusetts have taken the first steps in curing Down Syndrome (DS), by
silencing the extra chromosome that causes the disorder. Although the full treatment isn’t
perfected to ultimately cure those with DS, researchers are getting closer each day to doing so
(Sample, Ian). In addition to gene therapy’s progress is also its growing popularity among those
in the medical field and even patients. Many Boston area hospitals are willing to allow patients
to experiment with gene therapy. For example, a female patient, who is blind, is participating in
a trial to see if gene therapy is effective in treating blindness (Johnson, Carolyn). Overall, gene
therapy has proven itself to be effective in curing all kinds of diseases and disorders.
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