Causes

Although there are many theories about the cause of Parkinson’s disease, none has ever been proved. A few cases have been shown to be inherited and have been traced to mutations in four different genes, including the alpha-synuclein gene that Garvan is investigating.
The symptoms of Parkinson’s disease result from the progressive degeneration of neurons, or brain cells, in the midbrain. Neurons in the part of the brain that control co-ordinated movement release a neurotransmitter called dopamine. Dopamine stimulates motor neurons, those nerve cells that control the muscles. When dopamine production is depleted, the motor system nerves are unable to control movement and coordination. Parkinson’s disease patients lose 80% or more of their dopamine-producing cells by the time their symptoms appear.

Symptoms

Initially, symptoms are mild and often located on one side of the body. Although the rate of progression varies between individuals, the symptoms become more pronounced and spread to other parts of the body.

• Tremor (shaking) - This often occurs in the hands, fingers, forearms, foot, mouth and chin. Tremors typically take place when limbs are at rest
• Rigidity (muscle stiffness) - This often produces muscle pain that increases during movement
• Bradykinesia - Slowness in voluntary movement such as standing up, walking and sitting down
• Difficulty with balance - This occurs due to the loss of reflexes that help posture. Falling is common
• “Parkinson’s gait” - This common walk of a Parkinson’s patient includes a shuffling gait, drooped shoulders, lack of arm swing, head faced down and leaning backwards or forwards unnaturally. It is difficult to initiate walking and pausing mid-stride is common
• Micrographia (small handwriting)
• Lethargy and depression

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There are currently no laboratory tests to diagnose Parkinson’s disease definitively. A thorough neurological examination, including testing of reflexes, muscle strength and coordination is given, along with other tests, such as magnetic resonance imaging (MRI) and blood tests, to rule out the possibility of other diseases. As there is currently no cure for Parkinson’s, the symptoms are managed with a variety of treatments including drug and physical therapy.

Drug therapy aims to overcome the problem of depleted dopamine stores in the brain. Different drugs have different actions: some mimic the action of dopamine, some prevent further depletion and some enhance the action of the remaining dopamine stores. A neurologist will prescribe the treatment and dosage appropriate to the patient as severity and type of symptoms vary greatly between individuals.

In severe cases, neurosurgery may be necessary to relieve symptoms. Lesions are made on certain parts of the brain to interrupt involuntary movement. Deep brain stimulation, where an electrode is implanted in the affected area of the brain, may also help alleviate symptoms.

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Garvan is investigating Parkinson’s disease from a range of approaches. We have some scientists researching the mechanisms behind cell degeneration. We know that certain pesticides, toxins and genes (such as the alpha-synuclein gene) cause Parkinson’s disease, but why they cause the disease is not yet fully understood.

Garvan’s research investigates the mechanisms behind the release and control of dopamine in the brain. Once the various mechanisms are known, we can develop a therapeutic approach to treat the disease and restore movement control.

One of our most exciting research projects involves seeing how we can harness the brain’s own adult stem cells, which normally function to repair injury to the brain and make new nerve cell connections, to help treat Parkinson’s disease, as well as other neurodegenerative conditions.

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