1. An Overview of Conventional and Experimental Treatments
Parkinson’s Disease
An Overview of Conventional and Experimental Treatments

2. Background
Parkinson’s disease is a disorder that affects nerve cells in the part of the brain controlling muscle movement
Disease is progressive – signs/symptoms worsen over time
Eventually is disabling, but progresses gradually
Believed to be caused by genetics, environmental factors or a combination of the two

3. Parkinson’s Disease Stats
First desribed by James Parkinson in 1817
Affects ~1 million in the U.S.
Onset typically between years of age, and slowly progresses with age
Average onset is 62.4 years of age

4. Neurological Basis NORMAL BRAIN FUNCTION – Basal Ganglia
“Neurodegenerative Disease” : caused by degeneration (dysfunction and death) of neurons within the brain (nigrastriatal pathway of the basal ganglia)
NORMAL BRAIN FUNCTION – Basal Ganglia
Cells in substantia nigra produce/release dopamine
Dopamine released by SN neurons lands on neurons of other brain centers, controlling their firing
Main targets are caudate nucleus and putamen (striatum)
This basal ganglia pathway is involved in regulation of movement

6. Neurological Basis PARKINSON’S BRAIN FUNCTION–Basal Ganglia
Cells of substantia nigra degenerate
These cells can no longer produce adequate amounts of dopamine
Neurons of striatum, etc. are no longer well regulated, thus do not behave in normal manner
Results in loss of control of movements – leads to symptoms characteristic of Parkinson’s disease

8. Characteristic Symptoms
MOTOR
tremor
bradykinesia
rigidity/freezing in place
lack of facial expression
postural instability
stooped, shuffling gait
NONMOTOR
diminished sense of smell
low voice volume
foot cramps
sleep disturbance
depression
constipation
drooling

10. Conventional Treatments: Medication
LEVODOPA (L-DOPA)
precursor to dopamine, converted to dopamine by nerve cells in the brain
Treatment with dopamine not possible, because dopamine can’t cross blood-brain barrier
Generally combined with carbidopa (Sinemet) – helps levodopa get to the brain + reduces some side effects
Extended use often produces dyskinesias – uncontrolled movements (writhing, twitching, shaking) among other minor side effects

11. Conventional Treatments: Medication
DOPAMINE AGONISTS
not changed into dopamine, but rather act LIKE dopamine at brain synapses where dopamine is usually present (nigrostriatal pathways in Parkinson’s patients)
Used both as adjuncts to L-Dopa therapy and in younger Parkinson’s disease patients
Side effects similar to levodopa, but less likely to develop involuntary movements, more likely to cause hallucinations

12. Conventional Treatments: Medication
MAO Inhibitors (Selegiline)
COMT Inhibitors
Anticholinergics

13. Conventional Treatments: Surgery
Thalamotomy
Involves destruction of small amounts of tissue in the thalamus—major center for relaying messages/transmitting sensations
Can cause slurred speech and lack of coordination
Pallidotomy
electric current used to destroy small amount of tissue in the pallidum (globus pallidus)
May improve tremors, rigidity by interrupting pathway between globus pallidus and thalamus

14. Conventional Treatments: Surgery
Deep Brain Stimulation
implant device, pacemaker-like unit transmits impulses to electrodes placed in subthalamic nucleus
Produces same effects of lesion surgeries, but can be turned on and off

15. Experimental Treatment: Surgery
Fetal Cell Transplant Therapy
stem cells obtained via aborted fetus, grown in culture, transplanted into Parkinson’s patient at nigrostriatal pathway
New cells establish connections and “replace” cells originally lost, these cells function normally and even produce dopamine
Autologous “Self” Transplant
analagous to fetal cell transplant, except that precursor nerve cells are taken from patient and coaxed to produce dopamine, then implanted back into original patient
Reduces threat of autoimmune response and reduced “controversial baggage” associated with FCT therapy

16. Experimental Treatment: Surgery
Retinal Pigmented Epithelial Cell Transplant
Dopamine-producing cells taken from pigmented retinal epithelium
Mechanism of transplant analagous to fetal cell transplant therapy
If loss of contact from substrate, these cells die
Consequently, lower risk of aberrant integration—possible cause of dyskinesias seen in some FCT patients

17. Sources
Aminoff, M. (2003). Parkinson Primer: Overview of Parkinson’s Disease. Retrieved November 16, 2005, from
This source provided me with the most of the background information necessary in explaining the foundation of the disease. This source was especially helpful in determining the characteristic symptoms of the disorder as well as statistics.
Freed, C.R., Green, P.E., Breeze, R.E., Tsai, W., DuMouchel, W., Kao, R., Dillon, S., et al. (1994). Transplantation of Embryonic Dopamine Neurons for Severe Parkinson’s Disease. New England Journal of Medicine, 344, (7),
This source played a large part in writing the actual paper. In this article was information on the background of stem cells, implications in stem cell research, and most beneficial, the actual experimental procedure itself.
Lieberman, A. (2004). What is Parkinson’s Disease? Retrieved November 14, 2005, from
This source didn’t help much background information on the disease, but did help in providing an comprehendable version of the substantia nigra and its role in development of Parkinson’s disease. Also beneficial were the figures associated with this source.