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PARTNERS IN RESEARCH: CNDR || IOA || UDALL || Penn ADC
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Parkinson's Disease

Click here to learn more about CNDR's partner, the Penn Udall Center for Parkinson's Disease ResearchParkinson’s disease (PD), the second most common neurodegenerative disease after Alzheimer’s disease, is thought to affect about 1 to 1.5 million people in the United States, with approximately 50,000-60,000 people diagnosed each year. While it usually strikes people in their 50s or 60s, it can occur much earlier, and may progress for 20 years or more. The prevalence of PD increases with age, making it a common disease among the elderly.

Symptoms of PD

A diagnosis of PD usually is made on the basis of a patient’s symptoms. The three classic symptoms are muscle rigidity, tremor, and slowed movements (called bradykinesia). Other symptoms include instability, leading to balance and falls, and occasionally lack of movement (akinesia).  Affected people also frequently experience language and swallowing problems; changes in mood, behavior, thinking, and memory; fatigue (possibly resulting from uncontrollable movements); and sensory changes. In the later stages of the disease 20-40% of PD patients may develop dementia.

Why These Symptoms Occur

PD develops when a group of cells in an area of the brain called the substantia nigra begin to malfunction and die; these cells are responsible for the production of dopamine, a neurotransmitter that sends Click here to learn more about the cellular and molecular pathology of Parkinson's diseaseinformation to the parts of the brain that control movement and coordination. As the dopamine-producing cells die and the level of dopamine in the brain decreases, messages from the brain telling the body how and when to move are slowed more and more, rendering the person unable to initiate and control movement normally.

What causes the death of these cells? Examination of the tissue from PD brains reveals protein aggregates called Lewy bodies (LB), composed of a protein called alpha-synuclein along with other proteins. Lewy bodies are also found in other neurodegenerative diseases, particularly Dementia with Lewy Bodies (DLB) and a subtype of AD called the LB variant of AD (LBVAD).  Aggregates of misfolded proteins have been found in many neurodegenerative diseases, although it remains unclear what role they play in causing the death of neurons.

Cause of PD

The cause of PD is unknown in most cases. A small minority of cases have been linked to specific gene mutations, but in most cases no specific genetic abnormality can be found. Some evidence suggests that toxins in the environment may cause PD. In fact, in the 1980s, a group of drug addicts developed PD after consuming a batch of drugs contaminated with a neurotoxin called MPTP. The toxin was accidentally produced during the manufacture of a synthetic opiate called MPPP. This tragedy led to a better understanding of the pathophysiology of PD and the development of animal models for testing PD treatments. Pesticides and herbicides have also been suggested as possible toxins that could lead to PD.

Treating PD

Treatments are available that provide symptomatic relief, but there is no cure at this time. PD is most often treated by replacing the missing dopamine with a drug called levodopa or L-dopa. In the brain, L-dopa is converted to dopamine. L-dopa usually given in conjunction with other agents that either increase the potency and block formation of dopamine outside of the nervous system where it can cause adverse side effects such as nausea; drugs that enhance the effect of dopamine; or that slow its elimination from the body or release it into the blood more slowly, thereby achieving consistent drug levels. Other drugs for PD include dopamine agonists, which mimic dopamine’s effects. While nearly all people with PD will eventually need L-dopa, there are side effects, so other treatments such as dopamine agonists may be used initially. Also treatment is often needed for non-motor symptoms, such as depression.

Newer and Experimental Treatments

When PD can not be controlled with drug therapy, surgery may be recommended. Surgery may involve lesioning areas of the brain that are responsible for movement problems or deep brain stimulation of these regions. Experimental procedures to treat PD include cell transplant therapy, gene therapy, and the delivery of growth factors to affected areas of the brain.

Finding a Cure

Finding a cure for PD will require a better understanding of the mechanisms of the disease. Scientists at CNDR are studying several possible mechanisms that may explain how a mutation or toxin could cause the death of dopaminergic neurons. In the brains of people who died from PD, scientists have found abnormal accumulations of a protein called alpha-synuclein. Accumulation of alpha-synuclein in the brain leads to the formation of Lewy bodies. Exactly how these aggregates form and why they cause the death of brain cells is not known.  For example, the underlying defect may be an inability of the cells to dispose of alpha-synuclein aggregates.

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