Parkinson's disease is caused by the progressive deterioration of about half a million brain cells in the portion of the brain that controls certain types of muscle movement. These cells secrete dopamine, a neurotransmitter (chemical messenger). Dopamine's function is to allow nerve impulses to move smoothly from one nerve cell to another. These nerve cells, in turn, transmit messages to the muscles of the body to begin movement. When the normal supply of dopamine is reduced, the messages are not correctly sent, and the symptoms of PD appear.
The four early warning signs of PD are tremors, muscle stiffness, unusual slowness, and a stooped posture. Medications can control initial symptoms, but as time goes on they become less effective. As the disease worsens, patients develop tremors, causing them to fall or jerk uncontrollably. (The jerky body movements that patients with PD experience are known as dyskinesias.) At other times, rigidity sets in, rendering patients unable to move. About one-third of patients also develop dementia, an impairment of cognition (thought processes).
Treatment of Parkinson's Disease
Management of PD is individualized and includes drug therapy and a program that stresses daily exercise. Exercise often can reduce the rigidity of muscles, prevent weakness, and improve the ability to walk.
The main goal of drug treatment is to restore the chemical balance between dopamine and another neuro-transmitter, acetylcholine. The standard treatment for most patients is levodopa (L-dopa), which was first approved for use in 1970. L-dopa is a compound that the body converts into dopamine to replace it in the body and help alleviate symptoms. (Without dopamine, signals from the brain cannot "transmit" properly to the body, and movement is impaired.) Treatment with L-dopa does not, however, slow the progressive course of the disease or even delay the changes in the brain that PD produces, and it may produce some unpleasant side effects because of its change to dopamine before reaching the brain. Simultaneously administering substances that inhibit this change allows a higher concentration of levodopa to reach the brain and also considerably decreases the side effects.
A number of drugs were approved in recent years to improve the efficacy of L-dopa or slow the destruction of dopamine in the nerve cells, including anticholinergics, COMT (catechol-O-methyltransferase) inhibitors, and Deprenyl.
Surgeons are experimenting with fetal tissue transplants, neuroablation, deep brain stimulation, and pallidotomy (a neurosurgical procedure) as possible treatments.
BAN ON HUMAN FETAL CELL IMPLANTS LIFTED.
In 1993 then-President Bill Clinton lifted a ten-year ban on the use of federal funds to transplant tissue from aborted fetuses to the brains of patients with PD to try to correct the neurologic damage. The Reagan administration had issued the ban in fear that this use of fetal tissue would encourage abortions, which the administration opposed. Prior to 1993, however, some researchers, adamant about the possibilities of the surgery, had proceeded to conduct research without federal funds.
In 1998 Dr. Curt Freed, a neurobiologist at the University of Colorado Health Sciences Center in Denver, began conducting the first federal study on the effectiveness of fetal cell implants after the ban was lifted. Of the forty patients with PD in the five-year, $5.7 million trial, half received fetal tissues implants; the others received "placebo" operations, in which no fetal cells were implanted, as a control to determine the effectiveness of the real operation.
The placebo surgery, like the authentic surgery, involved cutting two oval holes in the skull and then closing the incision. During the surgery, which lasted about four hours, patients were awake; they were required to stay in the hospital for several days following the procedure. Those who had the placebo operation were given an opportunity for the real surgery the following year.
The concept of placebo surgeries caused some controversy. Spokespeople from the Parkinson Institute defended the need for the control group, and Dr. Freed claimed the procedure involved minimal risk. Still, some physicians questioned whether the research was ethical. They wondered if even highly educated and informed patients could fully understand and appreciate the risks associated with any surgery and especially those involved in neurosurgery (brain surgery).
In 1999 the Freed group released preliminary results from the study. One year after the surgeries, patients younger than age sixty who received the fetal implants showed significant improvement in their symptoms, whereas those older than age sixty years and those given the placebo surgery showed no improvement. In 2004, Dr. Cynthia McRae, of the University of Denver, published a report that revealed that participants in Dr. Freed's study who believed they had received the transplant surgery reported an improved quality of life twelve months after the procedure was done, regardless of whether they received the actual transplant or the placebo surgery. In addition, these self-reported benefits were supported by physical evaluations performed by doctors who did not know which treatment any individual patient had received.
THE FUTURE OF STEM CELL RESEARCH.
The election of President George W. Bush in 2000 prompted concern among human embryonic stem cell researchers. President Bush had expressed his opposition to this field of stem cell research throughout his campaign and through the early days of his presidency, and researchers expected him to reinstate the ban during his presidency. Researchers and patients hoping to benefit from treatment based on this promising area of scientific study were partially relieved when, on August 9, 2001, President Bush announced that federal funds could be used to conduct stem cell research on existing stem cell lines. His decision bans the creation or use of new embryos for federally-funded experimental purposes. This means that federal funds will not be completely withheld from researchers in this field, but it places significant limits on the scope of research that will be eligible for federal support.
The excitement and optimism about human embryonic stem cells centers on these cells' capacity to renew themselves and develop into specialized cell types. Unlike other cells that have predetermined roles and functions, such as heart or brain cells, stem cells can develop into nearly all the specialized cells of the body—with the potential to replace cells for the nervous system, heart, pancreas, kidneys, skin, bone, or blood.
Research is under way that uses stem cells to treat neurologic disorders by replacing diseased or malfunctioning cells in the brain and spinal cord. The results of this research could have life-changing consequences for people suffering from MS, PD, Alzheimer's disease (AD), and spinal cord injuries. Other research focuses on developing organs and tissues for transplantation because there is an urgent need for donor organs. Still other investigators are looking at ways to induce stem cells to become insulin-producing cells of the pancreas to treat diabetes.
FETAL PIG BRAIN IMPLANTS.
In late 1995 a team from the Harvard Medical School reported that transplants of fetal pig brain cells into the brains of rats relieved PD-like symptoms. Limited trials on human beings also have been successful. If future planned human trials are equally successful, the procedure could revolutionize the treatment of PD without raising the ethical and moral issues involved in stem cell research and fetal tissue transplants.
ELECTRODE IMPLANTS.
Another new procedure being tested is the use of electrical implants. Electrodes are surgically implanted in the brain and connected to a battery-operated device, also implanted in the body. The device allows patients to "turn off" the tremors that prevent them from performing the activities of daily living such as pouring a glass of milk and feeding themselves. One drawback is that the device's batteries must be surgically replaced every three to five years.
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