How hospice became big business. A new investigation in The New Yorker reveals an industry that at times puts profits before patients.
Every year, 60,000 people in the U.S. are diagnosed with Parkinson’s disease. The devastating neurological disorder occurs when cells in the brain don’t produce enough dopamine. Parkinson’s is marked by tremors, stiff muscles and slow movement. The exact causes are unknown but experts believe it’s a combination of genetic and environmental factors. For most patients, Parkinson’s gets progressively worse. Actor and Parkinson’s patient Michael J. Fox stars in a new TV show about a man living with Parkinson’s. As public awareness increases, Diane and a panel of experts discuss the reality for most patients and the latest treatments.
- Story Landis Director, National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health.
- Dr. Zoltan Mari Interim Director, the Movement Disorder Center at the Johns Hopkins School of Medicine; and director, National Parkinson’s Foundation Center of Excellence at Johns Hopkins School of Medicine
- Todd Scherer Chief executive officer, The Michael J. Fox Foundation for Parkinson's Research
Ask The Expert: Answers To Your Questions On Parkinson’s Disease
Is Parkinson’s caused by bacteria? Can you recommend resources for caregivers of Parkinson’s patients? Dr. Zoltan Mari, director of the National Parkinson’s Foundation Center of Excellence at Johns Hopkins School of Medicine, answered these listeners’ questions and more. Some questions have been edited for space and clarity.
Q: Can you discuss the possibility that Parkinson’s is caused by bacterial infections? I’ve read that things like Lyme tick bacteria can cause Parkinson’s. True? – From Jane via Facebook
A: There is no convincing evidence of a bacterial etiology for Parkinson disease. Some infections may produce parkinsonism, with very similar presentation to Parkinson disease. These include viral encephalitides, which are very rare. Between about the two World Wars there was an epidemic called “encephalitis lethargica” (von Economo disease), a suspected viral infection (they never actually managed to isolate the virus) which rendered thousands severely parkinsonian – kindly depicted in the movie “Awakenings.” However, no bacterial infection has been linked to Parkinson disease or parkinsonism. There are hypotheses related to an immune-mediated mechanism that might play a role, but Lyme disease specifically has not been linked to PD with credibility.
Q: Is there a good place to start looking for information so families of Parkinson’s patients can help their loved ones? Also, is there a diet that can help with the symptoms or side effects from the medication? – From Angel via Facebook
A: The NINDS, The MJFF, and the NPF all have significant and highly useful web presence to provide advice on all daily issues relevant to patient’s with PD and their families. For example, the NPF has a great selection of brochures to advise on a number of topics, including nutrition.
Q: I have restless leg syndrome, which is remedied with Vitamin E as opposed to prescription medicines. I’ve heard that RLS is a precursor to Parkinson’s. Is that true and, if so, is there anything that can be done earlier instead of later? – From Crys via Facebook
A: While RLS is related to PD (its prevalence is increased in PD compared to the general population; both PD & RLS can improve with dopamine agonist medications), the relationship is not clear at the moment. RLS does not appear to be a so called “prodromal” condition for PD and as far as we know, having RLS does not significantly increase the risk of PD later on. Another condition, REM Behavior Disorder (or RBD), however, is a well-known risk factor/prodromal condition.
Q: Linda Ronstadt has lost her ability to sing due to Parkinson’s. Do all singers who come down with Parkinson’s lose that ability? – From Kristin via Facebook
A: No. In fact it is somewhat unusual (albeit possible). Interestingly, the opposite situation can sometimes be seen, in which patients who have significant speech impairment can still sing.
Q: What is the latest on studies focused on nicotine, both as a treatment and from diminishing a user’s chance of getting Parkinson’s? – From Eric via website
A: Nicotine does not appear to be a good treatment for the symptoms of PD, the way for example levodopa is. However, it is being looked at as possibly reducing the risk of developing the disease or slowing down progression. Those putative effects (prevention, disease modification) have not yet been conclusively proven, but remain possible. It has been observed that those who smoke cigarette, while increasing their risks for diseases more deadly than PD, have a lower risk of PD than that of nonsmokers. Research is currently under way to investigate this further.
Q: Has there been any research conducted using herbs, vitamins and nutrition to treat and prevent Parkinson’s? – From Valencia via email
A: Unfortunately, research has been rather limited in this area. Therefore, for the most part we don’t really know for certain whether these natural agents may or may not have an impact on PD. It is probable they are not very effective. They may be safe though and usually inexpensive. Since the chances of them being highly effective are low, there remains little scientific or industrial interest in funding such research.
Q: I have a friend who has been diagnosed with something called “essential tremor,” and her doctor tells her that this was caused by a medication she takes for some other condition. However, she also exhibits some of the non-motor symptoms related to Parkinson’s you have discussed. What is the difference between Parkinson’s and “essential tremor?” Are the two easily misdiagnosed? – From Pam via email
A: Essential tremor is another disease, although its definition or even existence have been recently questioned and reviewed. In any case, ET is a disease much different from PD in that it is considered a mainly tremulous disease that does not display the classical parkinsonian motor symptoms besides tremor (slowness, stiffness). Whether imbalance is part of the ET phenotype is questionable, but more than likely yes. The rate of progression and the overall disability in ET is generally far less than PD. The tremor is different in that ET patients shake when they are moving and attempting to use their hands (such as holding a cup of writing), whereas in PD tremor is characteristically “resting”, i.e. worse when the hands are relaxed and tend to reduce when the hands are used in active tasks. Also, ET is often familiar, whereas PD is rarely familiar. ET is more common than PD.
The relationship between ET and PD is not fully known, but we do know that those who have ET are more than 4x greater likelihood of coming down with PD later in life than the general population.
The friend you are describing may or may not have ET, but ET is a primary idiopathic brain disease and is not caused by medications. However, there is another kind of tremor, which is called “exaggerated physiological tremor” and it is even more common than ET. Most tremor that’s seen as a medication side effect is of this variety and it can resemble ET very closely. Another common cause of exaggerated physiological tremor is hyperthyroidism and this is also the kind of tremor we all have if we drink too much coffee.
Q: We know that people who have hyperthyroidism have very little incidence of heart disease. Are there any known medical conditions which seem to confer some similar degree of “immunity” from Parkinson’s? – From Bob via Facebook
A: As mentioned above, it seems that patients who smoke may have a somewhat reduced risk of PD (of course no one should ever smoke thinking this protects them from PD as while that may or may not be true, what’s certain is that the downside from increased cancer risk far outweighs the putative PD protection benefits). Another recent observation is that people who exercise regularly could see their PD progression slow down or even have a slightly reduced PD risk. This is a very active area of research and many other environmental factors and possibly neuroprotective agents are being investigated in this context.
Q: I once watched a documentary on Lyme disease, and it claimed that upwards of 75 percent of people diagnosed with neurological diseases such as Parkinson’s also tested positive for Lyme disease. Can you elaborate on any connections between Lyme disease and other major neurological disorders such as Parkinson’s? – From Joe via email
A: Unfortunately the possible connection with Lyme disease has been blown out of proportion and this seems to be reflected in public awareness, as Lyme disease almost always comes up in every Parkinson Q&A often at the expense of more important aspects of the disease. There is no compelling evidence of a specific connection between Lyme disease and PD. PD has a specific pathology that is well described and has nothing to do with Lyme disease or the bacteria causing Lyme disease. Lyme disease is due to bacterial infection and can be treated with antibiotics. There have been a growing number of believers in “chronic Lyme”, a vague collection of syndromes attributed to some ongoing chronic pathology that may be responsible a large number of varied and mixed symptoms, but without a clear organic link. I am sorry to say that Lyme titers (serological biomarkers of active or past Lyme infection) have been misused to support these questionable theories. In any case, there are no controlled and high quality research studies to indicate that there’s a true increase in Lyme in PD patients and I doubt much effort will or should be devoted to this as there doesn’t appear to be any specific biological connection between (at least the idiopathic form of) PD & Lyme disease.
Q: I take two medicines that affect dopamine and wonder if taking these for decades could result in a higher likelihood of getting Parkinson’s? I have no family history of Parkinson’s or dementia, and have a healthy diet, exercise and also have (treated) hypothyroidism. – From Jen via email
A: Without the specifics, it is difficult to know. We do know that certain chemicals, such as pesticides & toxins (e.g. rotenone, paraquat, MPTP) can cause parkinsonism. I am not aware of any currently approved medications that also increase that risk. As mentioned before, however, exercise may reduce your chances of coming down with PD (and it is healthy anyway).
Q: My grandfather has Parkinson’s and was diagnosed with Lewy Body Dementia. Could you talk of any correlation and prognosis, and how to help? – From @aswathwood via Twitter
A: Some people believe LBD is a variant of PD. Both are so-called “synucleinopathies”, diseases where there is pathological processing of a protein called alpha-synuclein. When this protein misfolds and then aggregates within the cells it forms “Lewy bodies”, which can be seen both in PD and LBD. Clinically the distinction between LBD and PD is based on the timing of how motor and nonmotor problems appear relative to each other. If significant nonmotor problems (such as dementia or psychosis/hallucinations) appear within 1 year of the onset of motoric parkinsonism (such as slowing, loss of dexterity, imbalance, tremor, stiffness) then by definition the diagnosis is LBD. I don’t know the specifics of your grandfather’s presentation, but if he had classical PD presentation without much nonmotor problems (dementia/psychosis) for years and then started having these, clinically he doesn’t necessarily meet diagnostic criteria for LBD. In terms of how to help, the mainstay of therapy would be symptomatic. If he needs PD medications it is likely he would benefit from levodopa more than dopamine agonists if there is a concern about LBD or nonmotor problems reminiscent of LBD, as dopamine agonists tend to be very poorly tolerated in LBD. If nonmotor symptoms are causing much disability, those can be addressed. There are multiple different medications to enhance memory (such as donepezil) and which one and how much should be used must be highly individualized. Also, the psychosis can be often mitigated by atypical antipsychotics such as quetiapine and clozapine. Please note that other antipsychotics are contraindicated.
Q: Please discuss neuroplasticity and the benefits of exercise for Parkinson patients. – From @DawnDaria via Twitter
A: As I mentioned above, there is increasing interest in the benefits of exercise. It is possible it can reduce the risk of PD and it is even more possible it can slow down the progression of the disease. We do not know why exactly this is. That itself (the putative mechanism of action) is subject of intense speculation and research. There are some theoretical bases to support the idea of enhanced neuronal plasticity in exercise. It is known that neuronal plasticity doesn’t stop in youth, but continues to old age and it is a likely mechanism that is capable of offsetting some of the ongoing pathological damage from PD that destroys cells and networks. I expect that the area of exercise and its effects on PD, PD risk, and PD prognosis/disease course will remain a very hot area of research.
Q: What is hardest for primary caregivers about caring for someone with Parkinson’s, and how can caregivers be best supported by their family and friends? – From Kirsten via Facebook
A: It depends. Some recent research demonstrated that those who see PD patients all the time are more adept in recognizing common warning signs, problems, and more readily able to apply the best treatment options. Treating PD is non-obvious. Rather complex motor and nonmotor problems need to be managed in a constantly changing, dynamic environment throughout the progression of the disease, appearance of new problems, worsening of others, with medications’ side effects changing as well. While early stage and stable PD patients may be well served by regular checkups done at their PCP’s office, it is recommended that a Parkinson specialist (or with another expression “movement disorder neurologist”) evaluate the patient at around the onset of the problem (to ensure that the diagnosis is correct) and intermittently afterwards, especially if new problems emerge. I personally like to work with other providers, including general/community neurologists and PCPs, which may be geographically closer to the patient and can see the patient more often and I am happy to counsel them on PD management when complicated problems are encountered. Another option to help such checkups if there are geographical barriers is an emerging new way of conducting “virtual visits” through telemedicine.
MS. DIANE REHMThanks for joining us. I'm Diane Rehm. Parkinson's disease affects 1 million people in the U.S., nearly 10 million people worldwide. Public awareness of the neurological disorder has increased thanks to actor Michael J. Fox who stars in a new TV show about a man living with Parkinson's. Joining me to talk about the reality for most patients and the latest treatment options: Story Landis of The National Institute for Neurological Disorders and Stroke, Dr. Zoltan Mari of Johns Hopkins University Medical Center, and, joining us by phone from New York City, neuroscientist Todd Sherer.
MS. DIANE REHMHe's chief executive officer of the Michael J. Fox Foundation. I do invite you to join us as well, 800-433-8850. Send us your email to firstname.lastname@example.org. Follow us at Facebook or send us a tweet. Welcome to all of you. Thank you for being here.
DR. ZOLTAN MARIThank you. Good morning, Diane.
DR. STORY LANDISDelighted to be here. Thank you for asking us.
DR. TODD SHERERThank you. I'm glad to participate.
REHMAnd let's start with you, Dr. Mari. Explain to us what Parkinson's disease actually is and how it begins.
MARISo Parkinson's disease is a neurodegenerative disease. It is a progressive neurological condition that often starts with certain motor problems, movement control issues. It could be a little tremor, loss of dexterity, slowness or balance problems. And for the longest time, it has been recognized as a movement disorder because of those signs that oftentimes come on early.
MARIHowever, more recently, we recognized that it's not only a motor disorder. There's a very significant non-motor component as well, such as anxiety, sleep problems, depression, panic disorder, many other things that are not necessarily a movement control issue but relate to non-motor behavioral problems, which could be quite disabling, especially more advanced stages.
REHMAre we seeing more of Parkinson's, or are we simply hearing more about it?
MARII think it may be both. There are some data to suggest that actually there is an increasing prevalence of Parkinson's disease. There are a couple of factors to that. One may be the fact that we are an aging population, and the incidents of Parkinson's disease is age-related. So the older the population is, the more we're going to see of it.
MARIOver 60 years, it's about 1 percent of the population affected. So hundreds of years ago when the life expectancy was 40 years, obviously there were fewer individuals to have had a chance to get to that age range. So that's part of it, but there may be other factors as well that are somewhat exploratory and under investigation.
REHMOther factors, Dr. Story Landis?
LANDISSo one of the possibilities is that there are environmental influences which represent risk factors. Thirty years ago, everyone was convinced that Parkinson's disease was caused by things in the environment. That came from the observation that, after the flu epidemic in 1918, there were many cases of (word?) encephalitis, which exhibited itself as Parkinson's.
LANDISAnd then the observation that if you made a synthetic opioid incorrectly, you ended up with a toxin which killed dopamine neurons, which are lost in Parkinson's, and gave rise to the frozen addict phenomenon. But more recently, there are epidemiological studies which show that exposure to particular solvents can cause Parkinson's disease as can the exposure to pesticides or even herbicides and also traumatic brain injury can increase...
REHMAnd when you talk about these pesticides, herbicides, what are you talking about, things like DDT that have already been banned or those that are even now on the market?
LANDISThere are a number of those which are still in use. And, in fact, the data that support the role of pesticides, epidemiological data, come from studies of farm workers in the Central Valley of California.
REHMThe thing I want to say up front is that my own husband has had Parkinson's for the past eight years. He is now in assisted living. His began with, as you suggest, Dr. Mari, just the slight shuffle and physical symptoms of that sort. Dr. Sherer, do we know absolutely what happens in the brain when Parkinson's begins to exhibit itself?
SHERERWe don't really. Most of the motor symptoms of Parkinson's that we've been talking about are due to the loss of cells in the brain that produce a very specific protein -- chemical that's called dopamine. And we can treat a lot of the motor symptoms then by replacing the dopamine in the brain using some drug treatments.
SHERERBut we know that there's a lot more going on in the brain, and we also know that by the time someone is first showing those motor signs, the slight motor signs that Dr. Mari described, there's been already a significant degeneration or loss of cells in the brain. So the concept is actually that the disease process is probably beginning in the brain years before the demonstration of any of the symptoms.
REHMAnd yet, Dr. Mari, you talked about the older population, the fact that we are an aging population, and yet, at the same time, you see Parkinson's appearing earlier and earlier. And, of course, Michael J. Fox is one of those people. How do you explain that, Dr. Mari?
MARISo the age of onset is a spectrum. There are variations. The average age of onset is 62 years, but that means that patients may come down with Parkinson's disease earlier ages and later ages. I recently saw a gentlemen who was 79 at the onset of Parkinson's disease, which is very unusual. But then there are patients who come down at an earlier age.
MARII have a patient who first developed symptoms at age 11, and that patient happened to have a mutation, a PARK2 mutation, as well as a PINK1 the same time. So certain genes will make it much more likely to have the Parkinson's disease presented at an earlier age.
REHMGenes that are inheritable.
MARIThese genes are inheritable, but they don't have what we call 100-person penetrates. So none of the Parkinson's genes at the moment will mean a certainty that you will have the Parkinson's disease. Like, in Huntington's disease, if you have the abnormal gene, it's just a question of time before you have the disease.
MARIWhereas in Parkinson's disease, no matter which one of the genes -- because there are multiple -- you have, you may still live an old age and not have Parkinson's disease, which speaks to the factors that Dr. Landis pointed out in the environment. So there may be an interaction between the genes and the environment, or it may be an interaction between many different genes that will ultimately determine when you're going to come down with the symptoms or if you're going to develop Parkinson's disease at all.
REHMDr. Landis, how much is NIH doing on Parkinson's these days?
LANDISWe're doing a great deal, although, to be honest, it's not as much as we'd like to be doing.
REHMHow much money has been allocated?
LANDISSo the NIH is in FY-12, which is the last year for which we have good figures, invested $154 million. The number for FY-13 will almost certainly be less than that because, as you know, due to the sequester, the NIH lost $1.5 billion from its budget. We don't actually allocate money to any particular disease. We balance the scientific opportunities and the need and invest the money as wisely as we can across all the different diseases for which we are responsible.
REHMThough the symptoms, the outward symptoms, may be totally different for Parkinson's and, for example, Alzheimer's, Dr. Mari, what do you see in the brain that's different for Parkinson's?
MARISo, for instance, Alzheimer's disease is a slightly different kind of a neurodegenerative disease where it is susceptible neural populations that are attacked by this neurodegenerative process are different from Parkinson's disease. And, ultimately, we believe that pretty much every neuron in the brain at one point will be affected, but the one that are affected first will be different between different diseases.
MARIAnd as Dr. Sherer pointed out, the dopamine neurogenic cells in Parkinson's disease have been recognized very early on and somewhat specific to Parkinson's disease. There are some specific susceptibility of these dopamine neurons provide they go first, and that relates to the motor control and what we discussed earlier.
MARIBut as the disease progresses, more and more neural populations or cell populations get affected, and that brings new and different symptoms, including non-motor symptoms, memory problems, et cetera. In Alzheimer's disease, it is the structures and networks that are responsible for memory and cognition are the ones that are attacked first, and that's how the presentation, clinically, appears different.
REHMSo what you're saying is that the order of presentation is what determines whether one is diagnosed with Parkinson's or one is diagnosed with Alzheimer's.
MARIPretty much. But at the same time, there are clear molecular differences also. So if you go ahead and do some microscopic evaluations, you will see differences.
REHMAnd we'll get to more of those differences after a short break. We'll take your calls, 800-433-8850. Stay with us.
REHMAnd welcome back. Here is our first email for Story Landis who's at the National Institute for Neurological Disorders and Stroke. Dr. Zoltan Mari, he's interim director of the Movement Disorder Center at the Johns Hopkins University School of Medicine. And with us by phone, Todd Sherer. He's chief executive officer of the Michael J. Fox Foundation for Parkinson's Research.
REHMHere is an email from Lola. She's in Bethesda, Md. "I'd like to know," she says, "if there's any knowledge about Parkinson's and frontal lobe dementia. My husband began to exhibit inappropriate behavior almost as soon as he was diagnosed with Parkinson's in 2004. One of the first things we noted was his lack of empathy. He became abusive, used obscenities, which he had never done before. He also began to engage in compulsive eating. He became unaware of people around him. Eventually, he became violent. He's now in a nursing home." Dr. Landis.
LANDISThat's very sorry to hear of his progression. There's nothing that precludes a particular person from having more than one neurodegenerative disease at the same time. In fact, when you look at brains of patients who died with a diagnosis of Alzheimer's, it's very common to find a mixed dementia. The most common mixed dementia is the pathological finds of Alzheimer's with tau protein aggregates and amyloid deposits in addition to the kinds of changes that we recognize as the consequence of vascular dementia. That is...
REHMSo it can all merge at the same or different times.
LANDISRight. There are -- in that case, there are two difference processes which are leading to the loss of populations of nerve cells.
REHMBut how common is the behavior she describes, Dr. Mari?
MARISo I would like to add that it is also possible that it's frontotemporal dementia from the get-go. As I mentioned, the so-called non-motor systems are part of Parkinson's disease, but they're very unlikely to present early. So if she describes that these behavioral problems presented in the first year, my suspicion that it is not Parkinson's disease, as frontotemporal dementia, Lewy body disease, even Alzheimer's disease can produce Parkinsonism, which is not Parkinson's disease.
MARIIt's not the Parkinson's disease pathology. It's the appearance of Parkinsonism, shuffling gait, tremor, slowing. That can be seen in frontotemporal dementia. The early onset of the severe non-motor problems would raise the suspicion for FTD but also for Lewy body dementia, which by definition should have these significant non-motor behavioral problems within the first year of the appearance of motor Parkinsonism.
REHMYou know, what worries me is that sometimes patients diagnosed with Parkinson's disease can be given medications that may bring on those kinds of problems. For example, Requip is one of those, Dr. Mari.
MARIAbsolutely. We are balancing some of the side effects caused by the symptomatic therapy to treat the motor problems. And these side effects can be quite disabling as well. Every patient is different in their response both from the benefits' perspective as well as the side effects perspective may differ.
MARISo we sometimes try Requip. If that causes problems, fortunately, we now know what those are because at first the impulsive behaviors were not disclosed and not known to the clinicians. And that caused a lot of problems. Now we know the spectrum of side effects, and we are prepared. And if you're seeing them, we scale them back or discontinue the drug. And therefore we get rid of the side effects, and we try something else.
REHMAll right. Dr. Sherer, I'd like to know the goals of the Michael J. Fox Foundation for Parkinson's Research, what you're doing, where you believe you're headed.
SHERERSure. Thank you. So the Michael J. Fox Foundation was founded in 2000 by Michael J. Fox with a pure mission of trying to accelerate research towards a cure for Parkinson's disease. So our primary focus is to understand the needs that people living with Parkinson's disease have and then to support the research to lead to new treatments, to improve the quality of life of people living with Parkinson's and ultimately a cure for the disease.
SHERERWe have grown over the last 13 years, so we're now the largest nonprofit funder of Parkinson's research, funding over $350 million in Parkinson's research. And in parallel to trying to develop new treatments, both for the symptoms and then for something that could slow the progression, we're also working on a number of challenges across the field that impact our ability to do that. And one of the things that we're working on a lot -- actually also in collaboration with the work at NIH that's relevant to the last discussion -- are better markers and tools for the diagnosis and tracking of the disease.
SHERERRight now, Parkinson's disease diagnosis, as was just discussed, is purely based on a clinical evaluation. And it's not 100 percent accurate. And that can have an impact both for the current treatment of the disease, as was just discussed, where people could be put on inappropriate treatment based on their diagnosis. But also, that impacts our ability to develop new treatments. So we need to be able to better identify people that may benefit from some of the exciting treatments that are in development.
REHMAnd before we get to some of those treatments, talk about Michael J. Fox, how long he's had Parkinson's. And I think a lot of people are wondering how and why he's doing so well.
SHERERSo Michael was diagnosed with Parkinson's in the early 1990s, so it's been probably over 20 years. Parkinson's disease is very different in different people. That's one of the things we've also talked about today.
SHERERSome people seem to progress more quickly. Some people progress more slowly. Also people respond differently to medication. So Michael, like many other patients, works very closely with his neurologists to optimize the use of the available medicines and, fortunately, right now, is doing very well.
REHMI'm so glad to hear that, I must say. I interviewed Michael several years ago at a gala. He is the honorary chair of the Parkinson's Action Network Gala. And I must tell you, his movements at the time seemed uncontrollable. And now we see him on television in a sitcom. So I think a lot of people have questions about that, Dr. Sherer. I'm not asking you exactly what kinds of medications he's on. But to see him in this situation, I think, gives a lot of people either hope, or they're wondering what's going on here.
SHERERYeah, I mean, what you are describing in terms of some of those uncontrollable movements, those actually are a side effect of the medication. And it's kind of counterintuitive because Parkinson's disease is marked by slowness of movement. But then in response to some of the medicine, people can actually appear to have extra or be hyperactive.
SHERERAnd it's a constant challenge for patients to balance their medicine to get the optimal benefit in terms of improving their movement without dipping into these uncontrollable side effects. And this is something that right now for Michael, finding the right dosing and interactions with his doctor in terms of optimizing his medicine, he's finding a process that is optimizing the therapeutic benefit while limiting those side effects.
REHMWhat do you believe, Dr. Sherer, Michael is attempting to do with this program focused on a man with Parkinson's?
SHERERI think first at the highest level, Michael is just going about his work. And his message sort of comes from that, in that in the face of a disease or in the face of a challenge this is just one part of who you are. And you can continue to make contributions and to do things that you really love and enjoy. And for him, he obviously loves and enjoys being on television and acting. That's his career and his passion. And I think we have seen a great response from our Parkinson's community through this example that this is just one part of who you are, but it's not everything that you are.
REHMDr. Mari, I realize you do not know Michael J. Fox. You do not know his medical history or the kinds of treatment's he's had. But how typical is Michael J. Fox in the Parkinson's community?
MARII would like to emphasize that it is true that there is quite a bit of heterogeneity within the Parkinson's population. And in terms of the rate of progression, there are patients who are much more rapidly progressive and then are some who are slowly progressive. It is unusual to do that well 20 years into the disease, but it's not unheard of. So I would say that 1 percent or less of the patients can have that wonderful functional state 20 years into the disease. I've had patients like that, but it's very unusual.
MARINow, in terms of the management making a big difference, I'd like to again confirm what Dr. Sherer said, that adjustments and being properly medicated actually can make a big difference. The National Parkinson's Foundation was involved in a study which is called Quality Improvement Initiative whereby they show that across centers of excellence there have been significant differences in outcomes, how patients were doing. And these are patients who are treated all by experts with treatments that are currently available to all of us.
MARIAnd the difference how we are using those treatment modalities that are currently available can actually make a big difference how well our patients are doing. So that's a very important observation in considering that the majority of Parkinson's patients in the United States are treated by either primary care doctors or general neurologists. The general sense is that we can do much better as a whole to improve quality of life by appropriate treatment adjustments.
REHMDr. Zoltan Mari of the Johns Hopkins University School of Medicine, and you're listening to "The Diane Rehm Show." We have many callers waiting, and I do want to let you know that we may not be able to get to all of you today. We know you have lots of questions about Parkinson's. Dr. Mari has graciously offered to answer questions from listeners that we don't get to during the hour. So please send questions on email, Facebook, Twitter or our website, and those questions and answers will be posted later at drshow.org. Let's go first to Columbus, Ohio. Hi there, Bob, you're on the air.
BOBHi, how are you?
REHMI'm fine, thank you.
BOBThat's good. I called because I have Parkinson's. I was diagnosed in 2000. I had DBS surgery in 2006. And now, even though my voice is weak, I can still do Tai Chi every day, and I teach a Taekwondo class for kids still. And I've been standing on one foot since you called my name.
REHMBob, I'm so glad that you're doing so well and that you are continuing with your Tai Chi. He talked about deep brain stimulation, Dr. Landis. And that has become somewhat controversial. Talk about the uses where it makes sense and where perhaps it does not.
LANDISSo deep brain stimulation is a treatment that is often suggested to patients who are in the mid-stage of the disease and are no longer well controlled by treatments which replace dopamine. NINDS, in collaboration with the Veterans Administration, ran a trial comparing DBS with best medical treatment and provided -- and that trial provided compelling evidence that in fact for many patients DBS was of significant benefit, better than just best medical treatment. And there are examples of patients whose lives have been transformed.
LANDISOne of the critical issues is where in the brain the stimulating electrodes are placed. In some cases placement isn't optimal and there are side effects rather like those which were described for Requip with compulsive behaviors. And we don't have long term follow up of those patients yet who have gotten DBS.
REHMInteresting. And how long would you like that follow-up to be?
LANDISWell, the NINDS and the VA are following those patients who were initially followed for three years for an additional five years in order to look at the long-term cost benefit analysis.
REHMDo I understand correctly, Dr. Mari, that once the physical symptoms have begun that deep brain stimulation only works on those movement parts of the disorder?
MARIThat is generally correct. And that underlines the important of patient selection because DBS is a symptomatic therapy. It is excellent to treat certain symptoms and can really be life changing, just as Dr. Landis mentioned.
REHMOK. Tell me about those symptoms.
MARISo, for instance, if somebody as tremor and that is very disabling to them and sometimes it is not very well controlled with medication, DBS can still help. Another very good example is, as Dr. Landis pointed out, at a certain stage of the disease we are no longer able to control the patient's functionality with adjustments of their drugs only.
MARIAnd that is because the so-called therapeutic window is narrowed. So the patients need more and more of the medications to be able to move and move around, but it takes less and less for the medication to cause these jerky movements dyskinesias. Those are great patients for DBS.
REHMAll right. And a short break here. When we come back, more of your email, your phone calls. Do join us, 800-433-8850.
REHMAnd welcome back. We'll go right to the phones to Susan in Cary, N.C. Hi, you're on the air.
SUSANHi, Diane, thanks so much for taking my call.
SUSANMy father was just recently, a couple weeks ago, diagnosed with Lewy body dementia. I had never even heard of it. And my understanding is that it's an Alzheimer's and Parkinson's type of mix. So it's, like, the, you know, the best of both worlds. And I just was wondering if we could speak about why most -- why we always -- I know we hear about Alzheimer's and Parkinson's, and that's where the research is going.
SUSANBut you never hear about LBD. Is the Michael J. Fox Foundation -- do they focus at all on LBD? And as well as -- I know you touched on it just a little bit ago, but about the medications and how it does affect each patient individually and how there are severe side effects.
REHMAll right. All right, Dr. Sherer, I'll start with you.
SHERERSure. Well, thank you, Susan, for the call. And so one of the things that we have been talking about is actually, I think, these diseases are all operating on a continuum, and there's some very similar processes going on in the brain and the underlying difficulties that are facing the physiology. And the diagnoses is still sort of unclear, so it depends somehow -- sometimes on what symptoms are being expressed at what time of the disease.
SHERERIn terms of our work at the foundation, many of the therapeutic strategies that are being developed for all of these Parkinsonism types of diseases will potentially have impact across the different diseases. So Parkinson's disease itself could sometimes be marked by cognitive problems. Lewy body dementia has mostly the same underlying biological problems that are happening in Parkinson's. So there's a lot of interaction and cross talk about the research that is going on across these diseases.
REHMAnd, you know, we haven't talked about the symptoms of freezing in the same extent that we've talked about the tremors, Dr. Mari.
MARISo freezing of gait is a common problem in Parkinson's disease, a difficult problem. Gait impairment and disorders include balance problems, slowing, many other things, but freezing of gait in particular is hard because oftentimes it is medication resistant. So the medications that otherwise help symptomatically with many other things won't really help freezing of gait. And, at the same time, as we discussed DBS, which could be so helpful in many things, it may not be helpful for everything. And freezing of gait tends to be one resistant problem, such as speech, as the gentleman earlier noted.
REHMHis voice muscles were weakening or freezing?
MARIThe muscles that create sounds are very a highly coordinated and sophisticated manner and that coordination is affected by Parkinson's disease. You're not able to project as well the -- it becomes hypo phonic or the volume of the voice goes down, but in more severe cases the articulation can also become a problem. So it's a combined speech problem in Parkinson's disease.
REHMAnd isn't there also ultimately, Dr. Landis, a swallowing problem?
LANDISYes, absolutely. And there are efforts to develop devices that will enable Parkinson's patients and other patients with swallowing problems to be able to swallow because, if you don't swallow, you will have the potential of pneumonia.
REHMAll right. Let's talk about going forward, what you're all hoping for. Here's a tweet from John who says, "I'd like to know more about intestinal gel for Parkinson's that's currently in research in the U.S." Is that correct, Dr. Mari?
MARIYes, that is correct. It is under investigation in clinical trial. In some other parts of the world, it is already approved treatment. Basically it is just a different way of administering Levodopa, the name of this...
REHMOrdinarily known by the name of Sinemet taken orally.
MARISinemet is the most well-recognized brand name, but there are other drugs that have Levodopa, such as Stalevo and others, Parcopa. But nevertheless this treatment modality -- it's called LCIG or levodopa-carbidopa intestinal gel -- is delivered to a tube into the stomach which actually goes beyond the stomach and releases the gel in the intestines from a cartridge that the patient wears.
MARIAnd that has a tiny motor that controls the rate as the gel is delivered. The reason why this is very good is because part of the disability, patients in more advanced stages of the disease have, is the ups and downs, the unequal delivery of Levodopa. This helps correct that to some extent...
REHMSort of level it out.
MARIAnd the fluctuations are reduced. And this is just a more advanced and better way of delivering Levodopa.
REHMBut isn't there also the possibility of infection with that intestinal tube?
MARIIt is an invasive treatment.
MARIAnd, therefore, all the, you know, complications and risks as associated with it. But I think most people believe that the patients who are good for this treatment, the ones that -- who fluctuate the benefits outweigh those risks.
REHMDr. Landis, what is the most exciting new possibility out there for perhaps not only treatment, but prevention?
LANDISSo the Holy Grail for Parkinson's disease, as for any other neurodegenerative disease, is to stop progression and, even better, if we could prevent. And there are a number of very exciting activities underway now with the discovery of genes that can either cause Parkinson's in families or represent risk factors for people who have sporadic Parkinson's. We now have a whole series of potential targets for Michael J. Fox, for the NIH and for pharmaceutical companies to focus on to develop better treatments.
LANDISProbably the most exciting of these is LRRK2 kinase which was discovered to be the most common genetic cause of Parkinson's. And the nice thing about -- I mean, it's not nice if you have the mutation. But the nice thing for the future is that this is a -- what they call a druggable target, that there are ways that you could manipulate activity of this particular protein.
REHMAnd how would one identify that that target is there?
LANDISSo if you wanted to see if affecting that target were helpful the first place you'd start is in -- not with a patient, but with a simplified system. And the most amazing way that you can do that now is through the use of induced pluripotent stem cells.
REHMI don't know what that means.
LANDISOK, so these are cells that are made by taking a piece of someone's skin.
LANDISSo if you knew a Parkinson's patient who had a LRRK2 mutation, you'd take a piece of their skin. You'd put it in cell culture, and you would roll back its developmental clock to make it just like a human embryonic stem cell.
LANDISAnd then you can turn those pluripotent stem cells that you got from the skin into dopamine neurons -- the neurons that are first affected in Parkinson's disease -- and you can make hundreds or thousands or millions of them. And you could then use them to screen to see if you had something that you thought blocked or increased the activity of this kinase, whether or not it was really effective in these cells.
REHMDr. Sherer, what is the most exciting development that you are seeing? I know there's a research community meeting in New York even as we speak. What's the latest coming out from your research organization?
SHERERSo I would put this really in two categories. And one is to follow up on what Dr. Landis was just describing. Probably the most exciting opportunity we have to develop really transformative treatments for people with Parkinson's is building on our increased understanding of what might be causing the disease. So our current treatments are only able to mask the symptoms, but the underlying disease is continuing.
SHERERAnd what some of these new genetic findings, the LRRK2, another gene called alpha synuclein, what they are telling us is things fundamental to what's causing the disease process. And we now have therapies being developed, some that have just actually reached clinical testing that are trying to correct some of these genetic changes and address that underlying disease process.
SHERERAnd what's important is that even in people who don't carry or inherited the genetic mutation we know that some of these same genes, same proteins, are involved in everybody with Parkinson's, people with Lewy body dementia. So this is a really new, exciting area we've never really had in Parkinson's before.
REHMAnd I do want to let listeners know that the Fox Foundation has a website where you can find clinical trials in your area. That link is up on our website, drshow.org. Let's go now to Steve in Fort Myers, Fla. You're on the air.
STEVEThank you. I just want to share a quick personal story. My father was diagnosed at age 54 with Parkinson's in 1974 and first manifested when he was on the tennis court. When a ball was coming toward him, his feet would just move up and down as quick as possible but the next step -- to make any step toward the ball wouldn't happen. And he was quite frustrated, and then he was diagnosed.
STEVEAnd he continued for the next 16 years to work and function quite well and speak and everything, was -- you know, it wasn't -- you could tell there was something wrong, but he was under the L-DOPA Sinemet medication for several years. And then at age -- well, 1991, 16 years later, his symptoms turned for the worse.
STEVEAnd he was having, you know, freezing -- when he would get out of a car, he would halfway get out of the car, and he would freeze. And he would sit there for, you know, for literally hours, and he didn't want anybody to help him and figured he could do it. And he would be walking or standing. And all of a sudden he'd fall down and recover right away.
STEVEBut anyway he died at age 74, and he did live with it for 21 years.
REHMI'm sorry, Steve. Yeah.
STEVEWell, yeah, for 20, 21 years, and it's interesting that, you know, the term Sinemet and L-DOPA keeps coming up. And it seems that the basic same medications, with the exception of the few you were discussing a few minutes ago, I wonder -- apparently they -- are they more effective now than they were, you know, back 40 years ago, 30 years ago and...
REHMI think that's a great question, Steve, because it is the medication that we're still using, Dr. Landis.
LANDISIt is the medication that we're still using. And I think that underscores the importance of moving forward to identify strategies other than symptom management. NINDS hopes to fund a trial later this year that will look at the possibility that a calcium-channeled blocker rather like the ones that people take for hypertension will slow progression. There's evidence that dopamine neurons have susceptibility to calcium-channel -- calcium overload, and this is a possible treatment for that.
REHMAnd you're listening to "The Diane Rehm Show." Dr. Mari, you wanted to add to that.
MARIYes. I would like to inject a little bit of optimism because I think that it's not all the same. There have been quite significant advances in therapeutics, and even just Levodopa, the most potent medication for symptomatic control, it remains that. But the way it is delivered is different. As I mentioned, there's Stalevo which is a drug that combines the Carbidopa-Levodopa with another drug called Entacapone which makes the Levodopa effect longer lasting.
MARIAnd that has been helpful in many patients' case. We discuss the LCIG as a new delivery, and there is also a new medication that is hopefully coming next year to the market, another formulation of Levodopa, and it's called Rytary, which could last even longer. So there are some steps in making the therapeutics better, and it makes a difference. However, I do agree that disease modification or prevention is the Holy Grail.
REHMAs we have talked about Parkinson's, Dr. Mari, there may be many young people out there whose parent has had Parkinson's. Is there any way now to determine for people at a younger age whether they have that gene or not?
MARISo it is possible to screen for a number of these genes that I mentioned which have been associated with a higher risk of Parkinson's disease later in life. There is a 23andMe, a service which allows you to freely be tested. We don't usually recommend genetic testing for clinical management purposes because, as we discussed, we don't have a way of preventing or stopping it.
REHMTo stop, right.
MARIAnd we will treat Parkinson's symptomatically. But if somebody wants to know, there are ways. But, again, remember and be cautious that it's not a certainty. Even if you an abnormal gene that is associated with Parkinson's disease, it is not a certainty that you will have Parkinson's disease. So that is an important limitation here.
MARIBut, again, it is possible to get tested. And we do do some research studies where we look for patients who have genetic abnormalities because we can learn a lot, as we discussed earlier, about Parkinson's disease in general. And perhaps this will be a way to help with the cure.
REHMDr. Landis, how optimistic are you?
LANDISI believe that we have tools now in hand that will enable us to make much more rapid progress. Dr. Sherer referred to the fact that we have a much better understanding now than we've ever had before about the biochemical and molecular factors that result in the death of neurons. And we've also made an amazing discovery in the past year that, in fact, the toxic proteins that are responsible for the death of neurons in Parkinson's disease actually move from one cell to another.
LANDISAnd that may explain why, with time, more and more systems are affected. This is a new insight and it gives us another target to think about in terms of blocking progression because if we could stop the movement from one cell to another that could have a profound impact on progression.
REHMAnd briefly, Dr. Sherer, how optimistic are you?
SHERERI'm very optimistic. I think we're making significant progress. I think the other thing that we're seeing, too, is that people with Parkinson's and their families are getting more involved in research, as research partners and collaborators. And that engagement is also going to help us accelerate progress.
REHMTodd Sherer, chief executive officer of The Michael J. Fox Foundation, Dr. Zoltan Mari of Johns Hopkins University School of Medicine, Story Landis of the National Institute of Neurological Disorders and Stroke, thank you all so much.
REHMAnd, of course, we'll be taking your questions after the program. Go to drshow.org. Thanks for listening. I'm Diane Rehm.
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