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The following is the text that appeared in the August issue of "Healthy Cells" magazine which si publisheed here in Peoria, IL. Dr. Rick and I happen to be on the cover and the focus of severaal insidde pagges. Dr. Rick is Dr. Richard J. Weber, Ph.D Associate Professor of Imnuopharmacology and Microbiology Dept. of Biomedical & Therapeutic Sciences University Of Illinois Medical School-Peoria campus One Illini Drive P.O. box 1649 Peoria, IL 61656-1649 Dr. Rick Weber In press "Healthy Cells" August 2001 Parkinson's Disease Nationwide, as many as 1.5 million people suffer from Parkinson's, according to the Parkinson's Disease Foundation. Though the disease is found most often in patients over 50 years of aae, as many as 10 percent of patients afflicted with the so-called "young- onset" Parkinson's are under 40 years. About 50,000 Americans are diagnosed with Parkinson's yearly, according to the National Institute of Neurological Disorders and Stroke, which estimates that the total cost of health care for Parkinson's patients will exceed $5.6 billion this year. The disease is not fatal, but it reduces longevity. It also seriously impairs the quality of life and may sometimes lead to severe incapacity within 10 to 20 years. Parkinson's Disease is a life sentence, not a death sentence. What Is Parkinson's Disease? Parkinson's Disease is a slow, progressive disorder that affects movement, muscle control, and balance,. It occurs when cells are destroyed in certain parts of the base of the brain, where they send out fibers to other brain regions. An essential neurotransmitter (a chemical messenger in the brain) called dopamine is released in those regions. Dopamine is one of three major neurotransmitters known as catecholamines, which help the body respond to stress and prepare it for the fight-or-flight response. Loss of dopamine in certain brain recions is the primary defect in Parkinson's Disease. This loss negatively effects the nerves and muscles controlling movement and coordination, resultin- in the major symptoms characteristic of Parkinson's Disease, including tremor, rigidity and a loss of the ability to initiate controlled movement. During the late 1950s Dr. Arvid Carlsson studied experimental animals that had lost their ability to perform spontaneous movements. He then treated the animals with L-dopa (Sinemet), a precursor of dopamine, which is transformed to dopamine in the brain. The symptoms disappeared and the animals resumed their normal motor behavior. Carlsson realized that the symptoms in the animals he studied were similar to the syndrome of Parkinson's Disease. This led, in turn, to the finding that Parkinson patients have abnormally low concentrations of dopamine in certain brain regions. As a consequence, L-dopa was developed as a drug against Parkinson's Disease and today still is the most important treatment for the disease. Testimony to the importance of his work ahd discoveries and in recognition of advances in the understanding of Parkinson's disease was Carlsson's receipt of the Nobel Prize in Physiology or Medicine this year. Current Treatments and Procedures Drug treatments are increasingly effective in alleviating symptoms and even slowing progression of the disease. Over time, however, the side effects of many of these medications can be nearly as distressing as the disease itself, and the drugs may eventually lose their effectiveness. Surgical procedures may be appropriate for some patients when drug therapy no longer works. The neurosurgeon drills a small hole into the skull and inserts an electrode, which generates a current and heat to destroy small amounts of tissue in certain brain i-e-ions responsible for many Parkinson's symptoms. Suraical techniques do not cure the disease, however, and the primary benefit is to allow people to continue on L-dopa without incurring its side effects. Future Outlook What about transplanting a brain? Although farfetched, it is possible to implant cells into brain regions. Experimental approaches, which hold promise, involved the surgical implantation of brain cells'rich in dopamine to replace those cells which are lost. Fetal cells are the most appropriate tissue since they survive well and have the capacity to develop in the brain. A recent study by Freed and colleagues published in the New England Journal of Medicine showed mixed success using this technique, with only a few patients improving and, in some patients, the symptoms actually worsened. Four fetuses were needed to treat each patient. At 50,000 new cases per year and 1.5 million current cases, the use of fetal tissue to treat the disease is not logistically feasible. In addition, there are vexing moral issues surrounding the use of fetal tissue. Another approach is to stimulate the brain to heal itself or regenerate the lost dopamine producing cells. Up until about 15 years ago the "dogma" was that once the brain or nerve cells were lost, they were gone forever. Common sense dictates that this is false, since, if it were so, how would we experience new memories, think new ideas, or learn. The brain must have the capacity for generation and, therefore, regeneration. In recent years several "growth factors" have been identified and are being tested in experimental animal models of Parkinson's Disease as well as other neurodegenerative diseases. Recently, a group at Rush Presbyterian St. Luke's Medical Center in Chicago led by Dr Jeffery Kordower delivered a growth factor gene carried by a virus directly into the vulnerable brain areas in monkeys with experimental Parkinson's Disease. Improvement was seen in the growth factor treated animals but not in the control group. Although promising, there are also problems that have been seen with other experimental 'gene therapy' trials. Many people are concerned about eating genetically modified foods, let alone being injected with a genetically modified virus. Several years ago while working at the Surgical Neurology Branch, National Institutes of Health in Bethesda Maryland my colleagues Drs. Robert Plunkett, Scott Ewing and Alois Zauner tried a different approach to treat Parkinson's Disease. Plunkett was working with me to develop surgical techniques and cell handling procedures to maximize survival and function of transplanted cells into brain.'In the course of experimental implantation of cells into brain, we frequently noted an infiltration of leukocytes into the implantation site. Leukocytes or white cells are cells of the immune system and frequently thought of as important in protecting us from infections. However, another role of white cells is wound healing and removal and repair of effete or senescent tissue. I We reasoned that the presence of the cell infiltrate may be partly responsible for the behavior and motor improvement seen in our models of Parkinson's Disease. I said, "Let's do the experiment!" As the "neuroimmunologist" of the group it was my responsibility to provide the cells for implantation. Plunkett would implant them into the brain regions depleted of cells making dopamine. I decided to produce a mild inflammation in the peritoneal cavity of a rat, harvest the cells and use these for implantation into several rats with experimental Parkinson's Disease. Within a week the animals receiving activated leukocytes be-an to show improvement, continued to improve and showed sustained improvement up to thirteen weeks when the experiment was concluded. Not only did the animals have more dopamine in the depleted brain regions, but regrowth of the lost cell was evident. We are currently working on understanding the mechanism of this regeneration and improving the technique with the eventual goal of treating patients with Parkinson's Disease. Several advantages of our technique include the use of the'patient's own cells so there is no graft rejection problem, availability of tissue for transplantation and eliminating the moral issues involved as in the use of fetal tissue. Furthermore, the expense and complexity associated with gene therapy approaches would be reduced. The prospects for the future for the treatment and possible cure for diseases like Parkinson's are remarkable and only serve to encourage further research and sustained funding through government and private sources. Many dedicated scientists working in this area over the last 40 years have brought us to this brink. However, it is the patients suffering from the disease like Joan Blessington Snyder, Michael J. Fox and many others, and their couraoe and determination that should be an inspiration to us all. If anyone would like to recieve a copy of this magazijne-please send me your snail mail address. Dr. Weber's reseach is a reciepeint of part of the money raised from our golf tourntament. Joan Joan E. Blessington Snyder 49/11 http://www.geocities.com/joanbsnyder [log in to unmask] "Hang tough.....no way through it but to do it." 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