RUNNING HEAD: PARKINSON'S DISEASE

Parkinson's Disease: An Overview

Laura Welling
Salt Lake Community College

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I remember watching my husband's hand tremor while he tied his shoes. I tried to ignore
it as his hand shook when he poured the breakfast cereal. I wasn't really prepared when he was
given the diagnosis five years ago Parkinson's Disease. I believe I have been in denial for quite
awhile. Researching this paper has been very good for me. It has forced me to understand the
disease in ways I haven't before, in many ways I haven't wanted to. But learning more about the
disease process, the possible causes, the research being done, the treatments available now and
the prognosis has opened my eyes in a good way. I truly believe knowledge is power.
Parkinson's Disease is a chronic progressive neurological disease that affects a small area
of nerve cells in the brain known as the substantia nigra. These cells normally produce Dopamine,
which is a major neurotransmitter that, when working properly, coordinates smooth and balanced
muscle movement. Parkinson's Disease causes these nerve cells to become damaged or die, thus
causing the muscles to become slowed or abnormal. (Dauer, Przedborski, 2003).
The main motor symptoms of Parkinson's Disease are tremor, bradykinesia (slowness),
rigidity (stiffness) and balance problems. Although these symptoms are probably the ones you
think of when you think of Parkinson's, there are many other non motor symptoms that occur with
the disease including, but not limited to, sleep disorders, changes in thinking, constipation, low
blood pressure, aches and pains, bladder symptoms, sweating, sexual difficulties, soft or slurred
speech, weight loss, and fatigue (NewYorkTimes, 2014).
Psychiatric symptoms are common in Parkinson's Disease and occur in at least 20% of
patients (Papapetropolous, 2005). These include hallucinations, confused states, delusions,
paranoia, agitation, anxiety, and delirium. These symptoms often become worse as the disease
progresses. And, often, they are made worse by the same medications that are supposed to be

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treating the motor symptoms of Parkinson's Disease.

Although an early and accurate diagnosis of Parkinson's Disease is important in developing
a good treatment strategy it is important to note that there is no definitive diagnosis for
Parkinson's Disease. The only accurate diagnosis is done after a person has died and they can
autopsy the brain. So, even with the best neurologist, an accurate diagnosis is never 100 percent.
There are several other diseases which mimic Parkinson's Disease and often get
misdiagnosed as Parkinson's. These include, Corticobasal Degeneration (CBD) which is a rare
brain disease that affects walking, balance, mobility and vision. There is also Progressive
Supranuclear Palsy (PSP) which shows imbalance, frequent falls, and dementia. Finally there is
Multiple System Atrophy (MSA) which has the symptoms similar to Parkinson's Disease of
bradykinesia, poor balance, and fainting (Ben-Shlomo, Daniel, Hughes & Lees, 2002).
The past 25 years have seen a major expansion of knowledge concerning the cause of
Parkinson's Disease provided by an understanding of the genetic and environmental factors
involved. In most individuals, their illness arises with no known cause. However, 15% of
people with Parkinson's Disease report having a close relative with the disease. (Giroux, 2012).
People with an affected first-degree relative have at least a two times higher chance of developing
Parkinson's Disease (Giroux, 2012). By studying these families with hereditary Parkinson's
Disease, scientists have identified several genes which are associated with the disorder. So far,
five genes have been identified that are definitely associated with Parkinson's Disease. These
include, SNCA, which makes the protein alpha-synuclein. In brain cells of individuals with
Parkinson's Disease this protein forms clumps called Lewy bodies. Mutations of the SNCA gene
are found in early-onset Parkinson's disease (Cookson, Hardy & Lewis, 2008).
PARK 2 gene makes the protein parkin. It normally helps cells break down and recycle

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proteins. It is found in individuals with juvenile Parkinson's disease. PARK 7 makes the DJ-1
protein, which may protect cells from oxidative stress. It is found in early-onset Parkinson's
Disease. PINK 1, whose function is not known, is found in early onset Parkinson's Disease also
(Cookson, Hardy & Lewis, 2008).
Finally, there is the LRRK2 gene. This is the greatest genetic contributor to Parkinson's
Disease to date. It makes the protein dardarin. Mutations in this disease have been linked to
late-onset Parkinson's Disease ( Cookson, Hardy & Lewis, 2008).
There is also evidence that certain toxins in the environment may cause Parkinson's
Disease. Scientists have suggested that external or internal toxins may selectively destroy the
dopaminergic neurons, causing the disease. Some toxins that may be linked to Parkinson's
Disease include: manganese, carbon monoxide, carbon disulfide and other pesticides and
herbicides. (Wiley-Blackwell, 2008).
In trying to figure out what possible risk factors may have played a role in my husband's
disease, he realized that he once worked at a shop where he used the chemical tricholorethylene
(TCE) on a daily basis to clean off his arms. TCE is a chemical widely used in industry and also
found in drinking water and some soil. Gash and Slevin (2008) were conducting a Parkinson's
Disease study when they found that 3 of 14 people who had Parkinson's Disease reported
extensive exposure to TCE in their past. The authors acknowledged that while the study was only
a very small scale study, the results demonstrated a potential link between chronic TCE exposure
and Parkinson's Disease. They also did some studies on rats in which it was shown that TCE
exposure inhibited mitochondrial function in the substania nigra where dopamine is produced.
(Wiley-Blackwell, 2008).
Other risk factors include head trauma or gender. Men are affected two times as often as

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women. No one knows the reason why.

Perhaps the largest risk factor of all is age. Most people who develop Parkinson's
Disease are over 60. The risk of getting the disease increases with age.
It is an important thing to remember that a single exposure to any one of the factors is
probably not enough to cause Parkinson's Disease. It is most likely a combination of factors.
Luckily, there has been a lot of research going on and our understanding of the disease has
grown exponentially.
Positron Emission Tomography (PET) is a form of medical imaging that allows a 3D
image of your brain to be produced. This technique has been key in investigating brain structure
in Parkinson's Disease research. It is also allowing us to investigate the structures in the brain
where dopamine is produced. This could help us with gene therapy. For example, a dopamineproducing enzyme is currently being replaced in patients in clinical trials. Once these trials
conclude, PET technology could be used to track the movement and action of the genes, giving us
important clues about Parkinson's Disease (NIMH, 2015).
Research has improved our knowledge and ability to use gene therapy to alleviate
symptoms. Glial-derived neutrophic factor (GDNF) has been found to protect dopamine releasing
neurons. So far trials in humans have been limited but trials in primates have shown that GDNF
stimulates the body to produce GDNF naturally (Grinberg, Heldman, Hollander & Linder, 2014).
In other research, gene therapy, using stem cells, was found to improve the tremor, stiffness, and
other movement symptoms. This is very promising.
Stem cell research is a controversial topic to say the least. I believe that stem cell
research offers great promise for understanding human development and differentiation in ways no
other research method can and I think it brings hope for new treatments for Parkinson's Disease. I

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understand there are those who value human life from the point of conception and who believe we
should respect these cells and not use these new human lives for the sole purpose of
experimentation. However, I believe stem cells offer hope for all types of medical advances
because of their unique ability to grow into almost any kind of cell. Researchers believe that
transplanting embryonic stem cells into target cells in Parkinson's Disease patients may allow
regeneration of dopamine producing cells. This is both profound and promising.
Although there is no current cure for Parkinson's Disease, there are some treatments
which can help manage the symptoms. As far as medications go, the most effective Parkinson's
Disease medication is carbidopa-levodopa. Levodopa is combined with carbidopa. Carbidopa
delays the conversion of levodopa into dopamine until it reaches the brain. Nerve cells can use
levodopa to make dopamine and replenish the brain's dwindling supply. It helps in about threefourths of Parkinson's cases but not all symptoms respond equally to the drug. (Mayo Clinic,
2014). Bradykinesia and rigidity respond best while tremor may not fair as well. Problems with
balance and other symptoms may not be alleviated at all.
Dopamine agonists are used to mimic dopamine effects in the brain. They aren't as
effective as levodopa but they last longer in the system.
MAO-B inhibitors are also used. They help prevent the breakdown of brain dopamine by
inhibiting the brain enzyme MAO-B, which metabolizes dopamine. These medications can cause
hallucinations or other possible rare reactions (Mayo Clinic, 2014).
Catechol O-methyltransferase (COMT) inhibitors prolong the effects of levodopa therapy
by blocking an enzyme that breaks down dopamine (Mayo Clinic, 2014).
There are also anticholinergics that help with the tremor but often have many side effects.
Besides medication, surgery may be warranted. Deep brain stimulation (DBS) is a

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treatment where the surgeon implants electrodes into a specific area of the brain. A device called
an impulse generator or IPG, which is similar to a pace maker, is implanted under the collarbone
to provide an electrical impulse to a part of the brain involved in a motor function. It is the most
effective treatment, especially for people with severe tremors who have a hard time coping with
the side effects of Carbidopa-levodopa. (Dauer, Przedborski, 2003).
My husband's neurologist told us about the levodopa pump which has just been approved
by the FDA. It is a pump that is surgically planted in the abdomen. It provides a constant dose of
carbidopa-levodopa so the patient does not have to take the oral medication. They are hoping
this will be a possible alternative to people who have trouble taking the oral medication and do
not want brain surgery. (Shprecher, 2015)
Another thing his doctor told us about is a new treatment under study - a calcium channel
blocker isradapine which is currently used to treat high blood pressure. It is hoped that it will
slow the progression of the disease by producing healthier cells for a longer period of time.
Hopefully, it will improve the quality of life for Parkinson's patients (Shprecher, 2015).
The severity of Parkinson's Disease symptoms vary greatly from person to person.
Although it usually progresses very slowly, it will eventually affect every aspect of life from
social activities, work, to basic day-to-day routines. Accepting the gradual loss can be difficult.
Being well informed about the future can make it a little easier.
I do not know what tomorrow may bring for my husband. I keep hoping for new
medications and new treatments. I believe all I can do at this point it to stay informed and stay
positive.

References

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Ben-Shlomo,Y., Daniel S.E., Hughes A.J., Lees, A.J. (2002, April). The Accuracy of Diagnosis
of Parkinsonian Syndrome in a Specialist Movement Disorder Service. Brain: A
Journal of Neurology. 125(4) 861-870.
Cookson, M., Hardy, J., Lewis, P.A. (2008, September). Genetic Neuropathology of
Parkinson's Disease. International Journal of Clinical and Experimental
Pathology. 1(3) 217-231.
Dauer, W., Przedborski, S. (2003, September). Parkinson's Disease Mechanisms and Models.
Neurons. 39(6) 889-909.
Giroux, M.L. (2012, March). Is Parkinson's Hereditary? Retrieved from www.nwpf.org
02/15/2015.
Grinberg S., Heldman E., Hallander I., Linder C. (2014, May). Delivery of GDNF to the Brain
by Novel Nanovesicles for the Treatment of Parkinson's Disease. Neurology.
Mayo Clinic. (2014, May). Retrieved from www.mayoclinic.org/diseases-conditions/parkinsons
02/20/2015.
National Institute of Mental Health. (2015, January). PET Scanning in Parkinson's Disease.
Retrieved from www.clinicaltrials.gov 02/20/2015.
Papapertropoulos, S. (2005, July). Psychotic Symptoms in Parkinson's Disease. Journal of
Neurology, 252(7) 753-764.
Shprecher, D.R., personal communication, February 26, 2015.
The New York Times. (2014, July 27). Parkinson's Disease. New York Times. Retrieved from
www.nytimes.com 02/19/2015.

Wiley-Blackwell. (2008, January). Etiology and Pathogenesis of Parkinson's Disorder.

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Science Daily. Retrieved from
www.sciencedaily.com/release/2008/01/080107181340.htm 02/18/2015.