Research News: Parkinson’s Disease

What is Parkinson’s disease?
Source: National Institute of Neurological Disorders and Stroke

Parkinson’s disease is a common progressive neurological disorder that results from degeneration of nerve cells (neurons) in a region of the brain that controls movement. This degeneration creates a shortage of the brain-signaling chemical (neurotransmitter) known as dopamine, causing impaired movement. Parkinson’s disease was first formally described in "An Essay on the Shaking Palsy," published in 1817 by a London physician named James Parkinson, but it has probably existed for many thousands of years. Its symptoms and potential therapies were mentioned in the Ayurveda, the system of medicine practiced in India as early as 5000 BC, and in the first Chinese medical text, Nei Jing, which appeared 2500 years ago.

What are the symptoms of Parkinson’s disease?

Usually the first symptom of Parkinson’s disease is tremor (trembling or shaking) of a limb, especially when the body is at rest. The tremor often begins on one side of the body, frequently in one hand. Other common symptoms include slow movement (bradykinesia), an inability to move (akinesia), rigid limbs, a shuffling gait, and a stooped posture. People with Parkinson’s disease often show reduced facial expression and speak in a soft voice. Occasionally the disease also causes depression, personality changes, dementia, sleep disturbances, speech impairments, or sexual difficulties. The symptoms first appear, on average, at about age 60, and the severity of Parkinson’s symptoms tends to worsen over time.

How many people are affected?

In the United States, about a million people are believed to suffer from Parkinson’s disease, and about 50,000 new cases are reported every year. Because the symptoms typically appear later in life, these figures are expected to grow as the average age of the population increases over the next several decades. The disorder is most frequent among people in their 70s and 80s, and appears to be slightly more common in men than in women. Parkinson’s disease is found all over the world. The rates vary from country to country, but it is not clear whether this reflects true ethnic or geographic differences or simply variations in data collection.

What causes Parkinson’s disease?

There are many theories about the causes of Parkinson’s disease. Researchers have reported families with apparently inherited Parkinson’s disease for more than a century. Until recently, however, the prevailing theory held that one or more environmental factors caused the disease. Severe Parkinson’s-like symptoms have been described in people who took an illegal drug contaminated with the chemical MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and in people who suffered a particularly severe form of influenza during an epidemic in the early 1900s. Studies of twins, and of families where Parkinson’s disease is common, have suggested that some people have an inherited susceptibility to the disease that may be influenced by environmental factors. In the fall of 1996, a collaborative study headed by scientists at the National Human Genome Research Institute (NHGRI) and the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health reported strong evidence that a gene on chromosome 4 can lead to Parkinson’s disease in some families. In June 1997 NHGRI researchers described how they found the gene and identified a specific defect in it that causes Parkinson’s disease in these families. The NHGRI researchers suspect that the abnormal gene may account for only a small proportion of the total number of Parkinson’s disease cases. But this gene and other similar genes that are known to exist elsewhere in the human genome are now expected to help scientists decipher additional causes of Parkinson’s and perhaps shed light on other devastating and common brain disorders such as Alzheimer’s disease. Parkinson’s disease, the researchers say, may be one of a group of neurodegenerative disorders in which the body’s normal cell mechanisms for breaking down protein go awry. This defect then leads to the accumulation of debris that clogs brain cells, eventually becoming severely disabling and ultimately deadly to these cells. The researchers propose that there may be several ways of getting to this final common pathway in which proteins form abnormal aggregates that can damage neurons. Sometimes the triggering event might be a defect in the gene that produces the protein, as in the families they studied. In other cases an infection, such as a virus, might alter the protein. A third possibility is some other kind of environmental insult or toxin that twists the protein into an abnormal shape and block normal protein breakdown. These possible environmental causes have not yet been firmly identified.

How is Parkinson’s disease diagnosed?

Parkinson’s disease is usually diagnosed by a neurologist who can evaluate symptoms and their severity. There is no test that can clearly identify the disease. Sometimes people with suspected Parkinson’s disease are given anti-Parkinson’s drugs to see if they respond. Other tests, such as brain scans, can help doctors decide if a patient has true Parkinson’s disease or some other disorder that resembles it. Microscopic brain structures called Lewy bodies, which can be seen only during an autopsy, are regarded as a hallmark of classical Parkinson’s disease, although they are occasionally found in other neurodegenerative disorders as well. The NHGRI scientists theorize that Lewy bodies may contain aggregated proteins. Autopsies have uncovered Lewy bodies in a surprising number of older people without diagnosed Parkinson’s disease–8% of people over 50, almost 13% of people over 70, and almost 16% of those over 80, according to one study. Some experts believe Parkinson’s disease is something of an "iceberg phenomenon," lurking undetected in as many as 20 people for each known Parkinson’s disease patient. A few researchers contend that almost everyone would develop Parkinson’s disease eventually if they lived long enough.

What treatments are available?

There is no cure for Parkinson’s disease. Many patients are only mildly affected and need no treatment for several years after the initial diagnosis. When symptoms grow severe, doctors usually prescribe levodopa (L-dopa), which helps replace the brain’s dopamine. Sometimes doctors prescribe other drugs that affect dopamine levels in the brain. In patients who are very severely affected, various kinds of brain surgery have reportedly been effective in reducing symptoms. These surgical approaches include pallidotomy and implantation of an electrical stimulator to counteract the effect of the loss of dopamine-producing cells in the substantia nigra. Another kind of brain surgery, in which healthy dopamine-producing tissue is transplanted into the brain, is also being tested. Finally, researchers are trying to discover substances that will prevent dopamine-producing brain cells from dying. Now that it is possible to identify individuals in some families genetically prone to developing Parkinson’s disease, scientists plan to test methods of halting or at least delaying the disease’s progression.