Jog for Jim 5K
"Outpacing Parkinson's"

About Parkinson's Disease

Thank you to the Michael J. Fox Foundation for providing this information.

What is Parkinson's?
Parkinson's disease is a chronic, progressive disorder of the central nervous system that belongs to a group of conditions called motor system disorders. Parkinson's is the direct result of the loss of cells in a section of the brain called the substantia nigra. Those cells produce dopamine, a chemical messenger responsible for transmitting signals within the brain. Loss of dopamine causes critical nerve cells in the brain, or neurons, to fire out of control, leaving patients unable to direct or control their movement in a normal manner.

Parkinson's disease has been known since ancient times. An English doctor, James Parkinson, first described it extensively in 1817; the thoroughness of his analysis is such that researchers and clinicians are still urged to read his original notes on the condition.

What are the symptoms?
Symptoms of Parkinson's, which often appear gradually yet with increasing severity, may include tremors or trembling; difficulty maintaining balance and gait; rigidity or stiffness of the limbs and trunk; and general slowness of movement (also called bradykinesia). Patients may also eventually have difficulty walking, talking, or completing other simple tasks. Because Parkinson's has a wide range of early symptoms that are similar to other neurological conditions, diagnosis is often difficult unless the clinician has experience in the field.

The course of Parkinson's varies substantially. Some patients have relatively few troublesome symptoms for many years, while others have especially severe cases that leave them with little or no mobility in just a few years.

What causes Parkinson's?
Scientists have not yet found the exact cause of Parkinson's disease. Most believe that it is a combination of genetic and environmental factors, but no definitive data exist.

Who gets Parkinson's?
It is currently impossible to predict who will get Parkinson's disease or to prevent it from occurring. In general, both men and women are affected equally and symptoms first appear, on average, when a patient is older than 50. At least one million people in the United States are estimated to have Parkinson's; many of them, perhaps half, are thought to be undiagnosed.

A subset of Parkinson's called young-onset Parkinson's affects those under age 40. Although the condition is clinically the same, treatment options may differ.

The exact role of heredity in Parkinson's disease is not clear. There are relatively few families in which known genetic mutations cause the disease, but there are many more where the disease somehow "runs in the family." Most cases of Parkinson's are believed to result from a combination of genetic and environmental factors.

What are the available drug treatments?
There is no cure for Parkinson's disease. Drugs have been developed that can help patients manage many of the symptoms; they do not stop the disease from progressing, however. Parkinson's patients frequently experience dramatic swings in mobility and mood (known as being "on" or "off"), which may depend on the severity of their disease or the timing of their medication doses. Because each Parkinson's patient reacts differently to treatment, doctors and patients must work closely to find a tolerable balance between the drugs' benefits and side effects.

The first drug approved specifically for Parkinson's (in 1970)—and still the most commonly administered therapy—is levodopa (L-dopa), which is sold in the United States under the brand name Sinemet. Levodopa is taken up by the brain and changed into dopamine. In most patients, it significantly improves mobility and allows them to function relatively normally. As Parkinson's disease worsens over time, larger doses must be taken. The drug also has debilitating side effects for some patients, including dyskinesia (involuntary movements and tics) and hallucinations.

A number of chemicals such as carbidopa, the other active ingredient (besides levodopa) in the drug Sinemet, are able to prolong the effects of levodopa and help reduce its side effects. Carbidopa works by slowing the conversion of levodopa to dopamine in the bloodstream so that more of it reaches the brain. Comtan (entacapone), a so-called COMT inhibitor, has the same effect as carbidopa when taken along with levodopa. It blocks a key enzyme responsible for breaking down levodopa before it reaches the brain. Similarly, the drug deprenyl (in generic form or marketed under the brand name Eldepryl) can enhance and prolong the levodopa response by delaying the breakdown of levodopa-formed dopamine. (Tasmar, also known as tolcapone, is another COMT inhibitor, but it is now rarely used in the United States because it can cause severe or even fatal liver toxicity.

Other drugs work differently. So-called dopamine agonists such as Parlodel (bromocriptine), Requip (ropinirole), Permax (pergolide), and Mirapex (pramipexole dihydrocholoride) work directly on the target cells of the substantia nigra in a way that imitates dopamine. Dopamine agonists are often used in combination with levodopa.

Some people with Parkinson's disease take drugs called muscarinic antagonists, which include Artane (trihexyphenidyl) and Cogentin (benztropine). These may be particularly effective for parkinsonian tremor. Symmetrel (amantadine) is sometimes useful for tremor or for making levodopa work better, but exactly how it works is not clear. It may also dramatically reduce dyskinesia in some patients with this side effect.

Unfortunately, all drugs used to treat Parkinson's disease may have side effects. Although some people never experience such side effects, others are very sensitive to the medications and may be unable to tolerate them. Most commonly, the side effects of "antiparkinsonian" drugs are mental confusion, hallucinations, and dyskinesia. Because effective treatment of Parkinson's disease is often a matter of balancing beneficial effects of drugs against their side effects, many people prefer to see experienced specialists.

What about surgery?
Surgery is usually an option only for patients with severe or quickly debilitating Parkinson's disease that is not responding to other treatments. It is not normally recommended until all non-invasive therapies, including drugs such as levodopa, have been tried. Doctors are understandably wary about operating on the brain because it is the body's most sensitive organ—and the one in which any damage to cells is permanent.

A procedure known as a pallidotomy may be performed on patients with particularly aggressive Parkinson's or those who do not respond to medication. A pallidotomy consists of having a tiny hole drilled in the skull and using an electric probe to destroy a small part of the global pallidus, which most experts believe is overactive in Parkinson's patients. Pallidotomy is particularly effective for reducing the dyskinesia caused by medication. The relatively small percentage of patients who have disabling tremors in the hand or arm may benefit from thalamotomy, a surgical procedure in which a group of cells in a brain region called the thalamus is destroyed. Thalamotomy does not help the other symptoms of Parkinson's disease.

An alternative to destroying small regions of the brain is to use deep brain stimulation (DBS). This procedure involves implanting a very thin electrode into the brain and using small electrical pulses from a device similar to a cardiac pacemaker to stimulate the brain and block brain signals that cause Parkinson's symptoms. DBS may be used in the globus pallidus or subthalamic nucleus to improve motor function. Although this procedure is relatively new, early results look quite promising. DBS of the thalamus (thalamic stimulation) is particularly effective at relieving tremors.

It is important to understand that current brain surgeries do not cure Parkinson's disease; instead, they help to control symptoms. In addition, the success rate of surgery depends on the experience of the surgical team. Therefore, some people contemplating surgery may wish to only consider having it performed at one of the major medical centers that has extensive experience in Parkinson's surgery.
A number of experimental surgical treatments such as fetal-tissue transplants have been tried over the past several decades. While these procedures may benefit a small group of individuals, the techniques have not been perfected and are not widely available. Serious side effects have also been reported. For some, there may also be ethical issues associated with the use of fetal tissue.

What's the status of research into a cure?
Scientists' understanding of how the brain works has greatly increased in recent years, leading many observers to believe that a cure for Parkinson's and similar neurodegenerative diseases may be imminent. Others are more cautious, pointing out that even the most promising therapies will require several years of clinical trials and other studies to ensure safety and effectiveness. There is little doubt, however, that increased research (which can only be achieved through increased funding, both public and private) will hasten the discovery of a cure or therapies that can halt the diseases' progression. It is impossible to estimate when that will happen.

The most controversial research avenue currently being explored is based on so-called embryonic stem cells, which are undifferentiated cells derived from days-old embryos. Most of these embryos are the product of in vitro fertilization efforts. Researchers believe that they may be able to prompt these cells, which can theoretically be manipulated into a building block of any of the body's tissues, to replace those lost during the diseases' progression.

Similarly, there is hope that so-called adult stem cells, which are harvested from bone marrow, may be manipulated to work the same way. Fewer ethical questions surround this sort of research, but some scientists believe that adult stem cells may be more difficult to work with than those from embryos. Either way, the scientific community is nearly unanimous in arguing that their research efforts would be severely hampered if they were not allowed to work on all forms of stem cells.

Human studies of so-called neurotrophic factors are also now under way. In animal studies, this family of proteins has revived dormant brain cells, caused them to produce dopamine, and prompted dramatic improvement of symptoms.

Some scientists are analyzing the potential role of genetic and environmental factors in causing Parkinson's. Significant progress in discovering what causes Parkinson's disease will open an entirely new vein of intensive research into curing the condition.

What conditions are similar to Parkinson's?
Multiple system atrophy, sometimes called Shy-Drager Syndrome, and progressive supranuclear palsy are two disorders that share many features with Parkinson's disease. Unlike Parkinson's, however, these diseases progress extremely rapidly, and the medicines used for Parkinson's rarely provide much benefit. Also, other neurodegenerative disorders, such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease), and Huntington's disease, share the feature of progressive cell loss in one region or in one system of the nervous system without a known cause. Unfortunately, the current treatments for these diseases are inadequate.