State of the Science on Parkinson's Disease
1:30 pm US Eastern Time
Call Transcripts
Moderator: Steve Heilig, M.P.H.,Co-Director of CHE, Director of Public Health & Education, San Francisco Medical Society
1. Science Update: Pete Myers, Ph.D., CEO, Environmental Health Sciences, Co-Author, Our Stolen Future
I'd like to draw your attention to a fascinating new area of research on obesity. Last month I attended a workshop at the National Institute of Environmental Health Sciences, pulled together by Gerry Heindel, which looked at in-utero contamination and its effect on adult obesity. This is a body of research where there have been very scattered hints in the literature for the past ten years or so. Gerry and others will be issuing an RFP for new research to be done. At the meeting there was some fascinating findings presented. Probably the most striking were presented by Retha Newbold, whom some of you will know. Retha is one of the leaders in research on transgenerational effects of diethyl stilbestrol. Retha presented some results that show that DES, at levels beneath the levels where you begin to see the types of damage that we traditionally associate with DES, at extremely low levels, where rats, exposed in the womb grow up grotesquely obese. Their weight homeostasis mechanisms, the feedback systems, somehow have been highly disrupted. There are two avenues that are being researched on this front, one has to do with the process of forming fat cells. Now it's clear that several contaminants can interfere with adipogenesis in a way that increases the number of fat cells and the efficiency with which they take up fat. There's another line of research looking at how contaminants may be reducing leptin sensitivity in adulthood as a result of exposure in the womb. So that leptin, which is a hormone crucial to the feedback systems involved in controlling weight, where fat cells produce leptin, goes through the bloodstream, into the brain, shuts down appetite and increases metabolic rate. Obese rats are leptin insensitive, and obesity can be caused by exposure to certain contaminants. There are lots of questions to be asked about this. Clearly, we don't yet know how relevant this is to human obesity, but enough of the mechanisms are shared in common between experimental animals in use and humans to think that it's going to open up a very exciting new front, particularly because it begins to offer opportunities for intervention by reducing exposures.
Steve Heilig: This is particularly important information for anyone who follows the epidemiological news about obesity and all the resultant health problems. If it turns out that there is an environmental factor there, it will be somewhat revolutionary in terms of what to do about it. Pete also has a paper about gene and environment interaction in the new issue of San Francisco Medicine that will be fascinating for a lot of people on this call. That paper and others are now online at: http://www.sfms.org/sfm.
The topic today is Parkinson's disease, which takes its name from a British physician who was born in the 1700's named James Parkinson. We have three fantastic speakers on the call today. I would like to draw everyone's attention to the disease spreadsheet, Chemical Contaminants and Human Disease: a Summary of Evidence. Parkinson's Disease is in that database with some of the chemicals listed. With that we will go to our first speaker.
2. First Speaker: Dr Beate Ritz, UCLA Departments of Epidemiology and Neurology and the UCLA Center for Occupational and Environmental Health, Co-director of the NIEHS funded Center for Gene-Environment Research in Parkinson's Disease (CGEP)
I'm researching Parkinson's disease in a rather large, federally funded NIEHS study on genes and the environment. The environment of interest in my study is agricultural pesticide use. The reason we are doing this study is because over the past 15 years more and more epidemiologic studies have emerged that show that there's a possibility that pesticides are actually involved in the onset of Parkinson's disease. However all the early studies had to rely on nothing more than recall of exposure. So we would ask patients and controls whether or not, and when and how much and what type of pesticides they used throughout their lifetime. That's very difficult, you can just imagine how hard it might be, when you're 70 years old and diagnosed with Parkinson's, to remember what kind of pesticide spray you may have used when you were in your 30's and 40's. Just about all of the human studies had to do this. California has an incredibly interesting system, called the Pesticide Use Reporting System that was instituted in 1972 by law. All the agricultural users have to report what they apply, when they apply it and where they apply it. This information is computerized and we were able to get access to this system. My students and I have been working hard to plot these usage's of different pesticides throughout the Central California Valley. You may all know that in Central California we not only have a lot of crops growing, but we are also using about a quarter of all pesticides used in the U.S. This is a very highly agricultural, chemically intensive area. The hypothesis of this study is to see whether we can link up this pesticide-use reporting system to determine, in the patients that they're collecting over a five year period, and linking that up to what was sprayed in the vicinity of their homes and work places. Right now, this is what is on-going in my study.
We're also collecting blood samples that we will be testing genetically. The other part of this hypothesis is that not everybody may be sensitive or susceptible to these pesticides and chemicals, but that they may have a genetic susceptibility that causes them to react in the way that they do when they're exposed.
There's one specific pesticide known as paraquat, which is structurally very similar to the only known chemical that has been shown in animal experiments for a long time now to cause death of cells in the brain. That chemical is called MPP+, and paraquat, which is a very commonly used herbicide, looks just like it. There's also some other animal models of other pesticides that show that these other types of pesticides also influence brain chemistry in a certain way so that these dopaminergic cells that are very sensitive to oxidative stress may actually be damaged at a much higher rate cell types.
3. Second Speaker: Deborah A. Cory-Slechta, Ph.D., Director, Environmental and Occupational Health Sciences Institute, The University of Medicine and Dentistry of New Jersey and Rutgers University Chair, Department of Environmental and Community Medicine, Robert Wood Johnson Medical School
We have been working on experimental models of pesticides and their contributions to Parkinson's disease. We know that there are many, many pesticides out there that, unlike the organophosphates, these are pesticides that do act on the dopamine system in the brain, and it's the dopamine system that is dysfunctional and destroyed in the course of Parkinson's disease. So we know there are many out there that have action on the dopamine system.
We came at this with the hypothesis that Parkinson's disease is not going to be caused by exposure to a single pesticide, which is very unlikely. A single pesticide is just going to be one of a series of risk factors that will ultimately contribute to whether someone emerges with a Parkinson's disease phenotype. And indeed, we said, because there are multiple pesticides that affect the dopamine system, what about mixtures of pesticides all acting on this system at the same time. So this system is being hit at the same time by multiple pesticides all acting at different places in the dopamine system and thereby compromising its ability to homeostatically re-regulate itself. This would render the system more vulnerable, increasing levels of oxidative stress and ultimately killing cells.
We developed an animal model on that basis, using paraquat, which has structural similarity to MPP+. It is really not an environmental chemical, but an experimental tool. We used paraquat because we knew it acted on dopamine systems. In this case we combined it with another spongicide, called manib, that we knew also acted on dopamine systems. We found in animal studies, that we could take doses of each of these two, doses that by themselves had no effect, but when we put them together what emerges is a Parkinson's disease phenotype. Using that model we went on to show that it had virtually almost all of the characteristics of the disease. First of all, if you use this combined exposure in aging mice, you see a far greater vulnerability to its affects. That is, the magnitude of the Parkinson's disease phenotype is much greater. Here, I'm including the loss of those dopamine cells, which is really the hallmark of the disease.
We also asked about gene/environment interactions, because we have genetic models based on some of the known human mutations for the disease. When you combine these exposures with that genetic background you're able to markedly enhance the magnitude of the phenotype that emerges.
We also saw that males were much more sensitive than females. In fact, that's something that has shown up in the epidemiological literature. In some cases it's been attributed to the fact that if pesticides contribute to Parkinson's disease, it must be that males are more sensitive because they get greater exposures. But that wasn't the case in our experimental studies and we still see preferential targeting of males.
Finally, I think we have one of the only developmental environmental models that have ever come along. We took these same exposures and asked a couple of questions. If we imposed these during the course of development will it lead to a Parkinson's disease phenotype in mice later in life? And will it enhance their vulnerability later in life when they're re-exposed to pesticides? The answer to both of those questions was yes. You can build a model in which there is a phenotype that emerges as the animal ages and if you challenge them as adults, with pesticides, they're far more sensitive than animals that only get adult exposure.
We've now done one more thing, which is to say that we don't actually have to give these pesticides at the same time. We can do one exposure early in development and challenge the animal with the other one later in life and still find these kinds of marked enhancements in the Parkinson's disease phenotype. So, I think what the later studies show is that you can have cumulative neurotoxicity over the lifespan. You can have silent toxicity that is a dysfunction of the dopamine system that you don't even know about until some challenge comes along later in life.
So again, we're not saying we don't believe that Parkinson's disease is caused by exposure to a single pesticide. We really think these pesticides that we know act on the dopamine system are acting in conjunction with these other risk factors and are therefore contributing to the disease.
4. Third Speaker: Joan Samuelson, President, Parkinson's Action Network
I have had Parkinson's disease for eighteen years. The Parkinson's community is just starting to come into its own as an active entity, just as the science is in a way exploding. Parkinson's might be unique in the way it impacts the development of an advocacy community.
When you're diagnosed with Parkinson's you're told that there's a drug that will essentially take away the symptoms, which is a marvelous thing, and in many cases it's true. The drug commonly known as L-dopa will essentially substitute for the missing natural dopamine in the system and will return one to a more or less fully functioning state, initially. Then that functioning decreases. But for a significant amount of time, in most people, including me, the drugs do have that affect. For example, at eighteen years post-diagnosis, I haven't had a PET scan, but based on my symptoms I've probably lost quite a bit of my natural dopamine system. The science says that at the time of diagnosis, probably somewhere around 80% of the natural system is gone and the system has functioned without it for quite a while. So, I've probably lost substantially all of mine.
When I wake up in the morning, I'm pretty much frozen stiff. It takes about an hour for the drugs to take effect. At that point, I can get out of bed and with some limitations, go on with my day, take care of myself and function in a pretty demanding and high stress job. So, it's great news to know that there is this drug. But it is a losing struggle. I am pretty unusual in that my functioning is working this well and this late, post-diagnosis.
People are faced with what is, at the moment, a more or less, incurable, progressive, neurological disorder that becomes greatly disabling. At the same time, the neurologist doesn't really stress that ultimate bad news, because they are anxious to take away the pain of that diagnosis. So, they say, "don't worry about it, take this pill." The impact of that on advocacy is that people are able and quite anxious to hide their symptoms so that their life can go on as normally as possible. What that means is that the Parkinson's community is quite closeted, especially in the early years. So in terms of developing an advocacy community, there's this first segment of time in which, a person can take away their symptoms and does, and essentially hides the fact that they have Parkinson's. Then there's perhaps a window when they can still function well enough to get to Washington, for example, and walk around Capitol hill, before finally they're too disabled to do so. That was the situation I found when I started the network about 12 years ago. It was very hard to get people to come to Washington and very hard even to find people in the community. But, bit by bit, we had to do that because 12 years ago, there was very little funding for Parkinson's research by the federal government. The NIH reported that it was spending somewhere around $25 million for Parkinson's research, which as most of you know is really a pittance in biomedical research funding. As a consequence there was almost nothing being done. So, we began to get active and the funding started to increase. NIEHS centers were developed and Morris K. Udall Parkinson's Research Centers were developed. Funding was increased and a program was started at the Department of Defense and that began to fund some of these wonderful researchers like Beate and Deborah.
At this point funding is not what it needs to be. There's more work we have to do on this front to support the research, but it's far more robust than it was at the time. So, we're still a community in development and the news of these scientific developments of course spurs us on to try to do more.
5. Question and Answer, Comments and Discussion:
Jackie Hunt Christensen, Co-Director, Food and Health Program, Institute for Agriculture and Trade Policy (IATP), Parkinson’s Association of Minnesota:
I want to echo what Joan said about the stages of involvement. I was an activist before I became ill with Parkinson's. In fact I may have developed the disease as a result of pesticide exposure I got during my activism. I am doing everything I can through CHE to actively engage the Parkinson's community, not only legislatively, but also in speaking with their physicians about their own environmental exposure. Whether it's anecdotal or not, I think it's important to collect that information. I think it's really important to activate people in speaking with their physicians and being brave enough, even before you're obvious, like I am. I'm very diskinetic right now; I have a lot of involuntary movements. It's really important to raise more awareness, not only about the disease, but also about the links.
Paul B. English, Ph.D., M.P.H., Chief, Epidemiologic Investigations Unit Environmental Health Investigations Branch, California Department of Health Services:
Could you say anything about the bill pending in California legislature creating a Parkinson's disease registry and what implications would that have for research in this area? And secondly, can you comment at all on any research that has looked at any stable biomarkers, say DNA damage, or adducts from past pesticide exposures and any case control studies or any work that's being done in that area?
Beate Ritz: The bill that's pending right now is a bill that would allow us to collect Parkinson's patients information in California in the same way that the cancer registry collects information on cancer patients already in the state of California, for the last 15 years. I had been researching cancer before I came to the Parkinson's field and we know so much more about cancer because we've had these beautiful registries in Los Angeles since 1972. The registries allowed us to contact patients for research and asked them whether they wouldn't mind participating in these studies. We could then conduct these studies at a population basis, which means that every patient has a chance to enroll in this research and we're not just going to specialty centers where certain patients self-select themselves, which is not representative of all Parkinson's patients. We know very little about Parkinson's disease because we don't have registries like the cancer registry and it's so hard to find patients to enroll in the type of studies I'm doing.
Right now I drive through the Central Valley and meet with neurologists, one on one, and persuade them to send letters to their Parkinson's patients every six months, asking them to contact us. That's all I can do, we're not allowed to get names, we're not allowed to send letters about the study to anybody. Because of the rules and regulations about privacy, we have to beg physicians to do that for us. This is a very, very important law and I hope everyone understands the importance for a rare disease in populations. You cannot do this kind of research effectively unless you have a registry. Once you have a registry you can do amazing things.
There are no studies of biomarkers or DNA adducts in human populations out there right now that we could go after. However, for the organochlorine pesticides, we know that they're stored in the fatty tissues and that they have a very long physiologic half life of up to thirty years, depending on when you start and which ones you count. What I've been doing to validate our pesticide exposure model that comes from these reports on which we have data for what was applied in what agricultural fields around homes, was to create an exposure estimate for 50 people who lived in Kern County, based on this computerized model. We drew serum of blood and looked for DDE, which is a metabolite of DDT. We can see that our model predicts really well, high levels of DDE in the blood of these patients. So while our model predicts what we see in the blood as a marker, but there's no larger studies that look at markers and the disease yet. So that's how far we are.
Ashley Hotz: Glutothione is found to be at low levels in Parkinson's patients. Is there any evidence that pesticides destroy the body's ability to produce glutothione? And have you seen any research that shows that intravenous glutothione has really been helpful for Parkinson's patients? I believe David Perlmutter has tried that therapy and has promoted it in various papers.
Beate Ritz: Glutothione is an anti-oxidant and it is the major anti-oxidant in human cells. We have enzymes that convert the reduced glutothione back into the active form. In the population there is a distribution of people who have better and less well working enzymes that keep making these anti-oxidants. There are reports in the literature that some Parkinson's patients may have enzymes that work slower, converting back to the anti-oxidant than for other people, but these are really sporadic reports and I haven't seen really convincing evidence that that is true. Also just the slowness of that enzyme would never produce Parkinson's disease, but when you're challenged with an oxidant, and a lot of pesticides are oxidant, and you don't have enough anti-oxidant and the combination of the two may be able to cause the disease.
Deborah Cory-Slechta: I would just comment that lowered or altered levels of glutothione is only one of many differences between Parkinson's patients and non-Parkinsonian individuals. It is one of many different constituents of oxidative stress pathways. So focusing on just one piece of many different pathways in a therapeutic context seems like an unlikely strategy to be very successful to me.
Beate Ritz: I would completely agree with this. I think there are many things that have to come together and I don't think it works to just reduce it down to glutothione only.
Sandra Miller Ross, Ph.D., Health and Habitat:
Over a decade ago, I had heard that there was a relationship between the 1918 flu and people who subsequently got Parkinson's, can anybody comment on that?
Beate Ritz: That was actually described in Oliver Sachs' novel, Awakening, that was later made into a movie. It is true that this flu virus seems to have destroyed the dopaminergic system in a number of patients. But it did more than that; it actually caused, as far as I know, encephalitis, so it also destroyed other systems. So we know there are many ways to destroy a cell and one way could be a virus, such as this flu virus, when patients develop not just the flu, but encephalitis from the flu. Many people have looked for viruses trying to find the one virus that may cause Parkinson's disease, but I'm not aware of anyone that would point to just a virus right now. This doesn't mean that if another flu epidemic like 1918 happens and a certain number of people develop encephalitis that they couldn't also lose their dopaminergic system, but it's probably not the case for at least 99% of all current Parkinson's patients.
Pamela K. Miller, Director, Alaska Community Action on Toxics (ACAT):
Is there any evidence linking essential tremor to environmental exposures?
Deborah Cory-Slechta: I'm not aware of any strong evidence of such a link.
Pete Myers: If you go to www.protectingourhealth.org and search on essential tremor, you'll see that a paper came out in late 2003, which found some relationship between essential tremor and lead exposure, but I would agree with the speakers, there's not a lot of information out there.
Karen Florini , Senior Attorney, Environmental Defense:
I wanted to mention a different angle on this. Something that causes Parkinson's-like symptoms, although it does not cause Parkinson's per say, has long been known to be significant exposure to manganese. I've gotten involved with this because the same folks who brought us leaded gasoline are now making a manganese-based additive, which the EPA initially refused to approve because of concerns about potential health impacts. The EPA was then forced by a court to approve it on the grounds that the Clean Air Act doesn't actually permit the EPA to consider health affects when initially approving gasoline additives.
Partly because of adverse publicity there's relatively little use of this additive in the U.S. so far, but it is used in Canada. Researchers such as Dr. Donna Mergler have been doing some very interesting work up there showing increased incidents of Parkinson's like symptoms probably linked to MMT use. I'm not suggesting that MMT or Manganese causes Parkinson's, but it does produce similar symptoms. So folks who have an interest in these areas might want to be aware of that as well.
Rachel Massey: I understand that in the absence of registries it's hard to say much about this, but what is the picture of how Parkinson's rates have developed over the past several decades?
Deborah Cory-Slechta: I actually looked into that because we have heard conflicting stories. I think that it's very difficult to come up with any real assessment as to how those rates have changed over the years. Particularly if we're thinking about tying it, as we're trying to do, I've heard both sides of the argument, trying to tie it to the use of environmental chemicals, like pesticides. I don't think that the databases are sufficient to make those kinds of assessments yet. One of the arguments that I hear from some people is that our health is actually improved and our life span is longer at the same time that we've actually increased the use of chemicals. But I think at the same time that ignores the argument that medical techniques and therapeutics have also improved pretty dramatically. I personally don't think there's a good database to answer that question.
Beate Ritz: I agree with Deborah, that in the absence of a real registry, according to standardized protocol of the diagnosis of Parkinson's, it's really hard to say whether there really are any changes or not. However I did look at mortality rates, which are really bad for Parkinson's because it's only reported in a small percentage of Parkinson's deaths as the underlying cause of death. When you look at the national and the California death certificates between the mid-1980's and 90's, the underlying cause reporting doubled. Whatever that means. It could mean that people are reporting differently, but it could also suggest an increase. These are rates that are age adjusted, so you're factoring out the fact that the population gets older.
Deborah Cory-Slechta: The only other thing that I would be careful about is that there are lots of other things that have changed in our culture over the past 50 years, including diet, obesity, levels of exercise and everything else. All of those things are changing in a dynamic way across time and I think that enhances the difficulty of trying to sift out these relationships.
Beate Ritz: Yes but the simple question, "does or does not disease increase?" should be answered. And I think that is the most important reason to institute a registry, apart from the fact that the registry gives us an incredible tool to go after causal factors, but it will also tell us whether a disease is increasing or decreasing or stable.
Michael Lerner, Ph.D., President, Commonweal:
I want to comment on the extraordinary high quality of not only the presentations, but also the questions and the answers. This is really a model of a collaborative call for us. I wanted to ask a couple of related questions. One is whether the occupational and safety health literature provides any clues in terms of occupations, outside of pesticide exposures, that can give us any clues? The second question is related to Pam Miller's question about essential tremor, in a broad way. There are many diseases that ultimately turn out to be more than just a single disease, but a whole cluster of diseases or overlapping diseases. In Parkinson's, Jackie Hunt Christensen, who's really been a leader in environmental health, has early-onset Parkinson's. I wanted to ask whether Parkinson's is a fairly clear-cut disease, or whether it's a complex set of overlapping conditions that may move out toward conditions such as benign tremor? There's a website called http://www.wemove.org/ that's for people with different movement disorders.
Beate Ritz: I'm an occupational and environmental epidemiologist, so my specialty is through occupational studies. However, when you do an occupational study, what you usually do is assemble a large number of workers who are most likely exposed through similar kinds of agents. If you want to study Parkinson's disease, you have to study 100,000 to 200,000 of those workers, which is possible, but it's very resource intensive. There is some sporadic information in the literature on solvent use and possibilities of Parkinson's disease, but these were studies that were not large enough to really be very informative. There are studies out there suggesting some metals including manganese and some combinations of copper and lead exposures possibly contributing to Parkinson's. But we really need larger studies to solve the issues of what kind of occupations may have increased risks for Parkinson's. I know there's currently a large cohort of welders in the Scandinavian countries that one of my colleagues is going to use to look at Parkinson's disease. Those are studies that need to done in the future to solve this issue.
Michael Lerner: I have essential tremor, as do two of my brothers. The two brothers that have it are both DES sons, the brother who does not is not a DES son. I'm in the middle of conducting a cancer retreat at Commonweal with a co-leader, a psychotherapist, who's also a DES son and also has benign tremor. I don't believe this has been reported in the literature on DES sons. But since DES was one of the early endocrine disrupting chemicals to be identified it suggests that a kind of a broad perspective on the relationship between different movement disorders may help cast light on specific disorders such as Parkinson's.
Deborah Cory-Slechta: I think your point is well taken.
Beate Ritz: I agree. In my Central Valley study, our movement disorder specialists are seeing patients and we are classifying them according to lot of criteria and we can identify two different subgroups of patients that we would call either tremor dominant or akinetic/rigid in their phenotype. When we looked at the reported family history in those two groups, we see about double the ones that we would call tremor dominant according to their phenotype report essential tremor in their family history. The ones that have more of an akinetic phenotype have double the rate of family members with Alzheimer's disease in their family. I'm not sure that will lead to anything, but I think it's an interesting phenomenon and we will definitely follow up on it.
Sandy Ross: A lot of this sounds like the total bucket theory, that I remember first hearing from Jeff Anderson, in which all of our life experiences, good and bad, our exposures, our poisonings, go into this vessel and eventually it overflows and it overflows toward our genetic predisposition or to the intensity of our poisonings and exposures.
Deborah Cory-Slechta: That's the point I'm trying to make and I very much agree with that. I think that's why you see individual profiles of what a disease looks like. There's not a single model, there are many models and I think it reflects those differences that we all bring to the situation.
Karen Florini: Do you have any sense of what fraction of diagnosed Parkinson's has a known etiology and what fraction does not?
Deborah Cory-Slechta: Over 99% are considered sporadic of unknown etiology, only a small proportion is considered to be genetically related at this point in time. That's not to say there isn't some genetic predisposition that comes to the table. Right now, most of what we're concerned with is sporadic, unknown etiology.
Pete Myers: If we were to go and speak with practitioners, medical professional caring for people with Parkinson's, where does the research we've heard today fit on their radar screen?
Deborah Cory-Slechta: I'm not sure the animal research fits on it at all. I'm not even sure they're aware of it, although when we started doing this it certainly got a lot of press attention. I think they probably heard something about pesticides, but I doubt that it really enters into dealings.
Joan Samuelson: Well I think that's true. This research is very new, compared to other situations. These developments are within this decade. Lots of people are treated by general practitioners and if their neurologists are not Parkinsonologists, and this is a very specific part of a very broad field, brain disorders. I don't think much of it has trickled down at all.
Anthony J. DeLucia, Ph.D., Volunteer, Kingsport Tomorrow:
As someone who grew up in California, now living in Tennessee, I think the comments about the Central Valley and pesticide use clearly indicate that this is a national crisis. We're currently looking at many diseases that we could relate to built environment-related diseases. I just want to see if there's a similar sense among people, that the impinging upon of agricultural processes or occupational links. There are many situations in which our changes in lifestyles affect these things, but particularly the built environment ones, where we look holistically.
Joan Samuelson:
It's of course not just agricultural exposures and pesticides; the most vocal group talking about occupational exposures at our most recent public policy forum in DC was veterans. They were talking about their suspicion that their exposure, while in the military, played a role, for example the various exposures on an aircraft carrier and jet fuel.
Jackie Hunt Christensen: I spoke to a number of veterans at the forum, many of whom will be attending our Young-Onset Parkinson's Disease conference in St. Paul, Minneapolis, in July. Has anyone looked at the dopamine receptors being stuck open and might that have something to do with Turret's?
Deborah Cory-Slechta: The two go hand-in-hand because of the way the dopamine system works. When the system loses dopamine levels, which happens when the cells die off and they're no longer making dopamine; there are lots of consequences of that. One is that the receptors on the other side of the cleft, the space in which the dopamine has to go and act on those receptors, they also change function because they're not seeing their dopamine anymore. So initially they up-regulate, increasing their sensitivity to be more efficient, in terms of their use. The other thing that begins to happen, is that the remaining dopamine cells have to work harder to make up the difference, and so they're taxed to a greater degree. In some respects it's a little difficult to separate the receptor function itself. Certainly if you look at some of the imaging techniques that people do, changes in receptors and changes in dopamine transporters that take that dopamine back up into the cell, are affected in the course of the disease.
Michael Lerner: What are the major groups, other than Parkinson's Action Network, that work on Parkinson's, from either the fund-raising or the patient point of view? And within Parkinson's Action Network, how large are you and what's your organizational structure?
Joan Samuelson: There are several national organizations that have Parkinson's as their constituency. They all raise money for privately funded research and/or provide patient support. When I started the network there was no voice in Washington, or any other sort of advocacy effort. One of the lovely things about the developing advocacy in the community is that lots of self-starting operations are popping up around the country organized around things like state stem cell legislation. I think there are the beginnings of focus around the issues of Parkinson's and the environment and occupational exposures like the veteran's. But there really isn't any other organized effort Parkinson's specific or broader to neuro-degenerative disorders or brain disorders, that's active in Washington or very active at all at this point.
Because there are so many national organizations, when I started the Parkinson's Action Network I was trying very hard to get them all to get along and very intentionally didn't describe it as a membership organization. We were all hopeful that we would all merge together into one operation, which never happened. We have about 200 people who currently attend our annual our public policy forum. Our database and mailing list has about 15,000 maybe 20,000. Our website is www.parkinsonsaction.org.
Jeanette Meyers: We're out of time, so I would like to thank all of our speakers for joining us.
